Scholars@Duke
Ivan Spasojevic

Ivan Spasojevic

Associate Professor in Medicine
Medicine, Medical Oncology
Box 3839 Med Ctr, Durham, NC 27710
5317 Orange Zone, Duke Hospital South, Durham, NC 27710

Selected Publications

Treatment with Manganese Porphyrin, MnTnBuOE-2-PyP5+, Suppressed the Activation of Macrophages in a Mouse Intracerebral Hemorrhage.

Journal Article Pharmaceuticals (Basel) · April 8, 2025 Background: Manganese porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), improves neurologic deficits in experimental ischemic stroke and has the potential to serve as an adjunct with thrombolysis or thrombectomy in stroke patients. In 10-30% of stroke patients follow ... Full text Link to item Cite

Effective extracellular payload release and immunomodulatory interactions govern the therapeutic effect of trastuzumab deruxtecan (T-DXd).

Journal Article Nat Commun · April 2, 2025 Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) targeting HER2, exhibiting significant clinical efficacy in breast cancer (BC) with varying HER2 expression, including HER2-low and HER2-ultralow. However, the precise mechanism underlying ... Full text Link to item Cite

Design of an equilibrative nucleoside transporter subtype 1 inhibitor for pain relief.

Journal Article Nat Commun · December 30, 2024 The current opioid crisis urgently calls for developing non-addictive pain medications. Progress has been slow, highlighting the need to uncover targets with unique mechanisms of action. Extracellular adenosine alleviates pain by activating the adenosine A ... Full text Link to item Cite

Safety Evaluations of Rapamycin Perfluorocarbon Nanoparticles in Ovarian Tumor-Bearing Mice.

Journal Article Nanomaterials (Basel) · October 31, 2024 Nanomedicine holds great potential for revolutionizing medical treatment. Ongoing research and advancements in nanotechnology are continuously expanding the possibilities, promising significant advancements in healthcare. To fully harness the potential of ... Full text Link to item Cite

Data from: Unlocking the therapeutic potential of T-DXd (Enhertu): Insights into mechanisms of action in HER2-low cancers and immunomodulatory effects

Dataset · August 7, 2024 These data are produced by LC/MS/MS analysis of plasma and tumor samples collected in mouse tumor treatment studies, utilizing T-Dxd (Enhertu) is a novel antibody-drug-conjugate (ADC) targeting HER2. After development of fit-for-purpose assays on Shimadzu ... Full text Cite

A cluster-randomized trial of water, sanitation, handwashing and nutritional interventions on stress and epigenetic programming.

Journal Article Nat Commun · April 26, 2024 A regulated stress response is essential for healthy child growth and development trajectories. We conducted a cluster-randomized trial in rural Bangladesh (funded by the Bill & Melinda Gates Foundation, ClinicalTrials.gov NCT01590095) to assess the effect ... Full text Link to item Cite

Interplay between ATRX and IDH1 mutations governs innate immune responses in diffuse gliomas.

Journal Article Nat Commun · January 25, 2024 Stimulating the innate immune system has been explored as a therapeutic option for the treatment of gliomas. Inactivating mutations in ATRX, defining molecular alterations in IDH-mutant astrocytomas, have been implicated in dysfunctional immune signaling. ... Full text Link to item Cite

Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens.

Journal Article Sci Transl Med · August 9, 2023 The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, the outer membrane anchor of lipopolysaccharide and lipooligosaccharide in Gram-negative bacteria. The development of LpxC-targeting a ... Full text Link to item Cite

An injectable PEG-like conjugate forms a subcutaneous depot and enables sustained delivery of a peptide drug.

Journal Article Biomaterials · March 2023 Many biologics have a short plasma half-life, and their conjugation to polyethylene glycol (PEG) is commonly used to solve this problem. However, the improvement in the plasma half-life of PEGylated drugs' is at an asymptote because the development of bran ... Full text Link to item Cite

MnTnHex-2-PyP5+ Displays Anticancer Properties and Enhances Cisplatin Effects in Non-Small Cell Lung Cancer Cells.

Journal Article Antioxidants (Basel) · November 7, 2022 The manganese(III) porphyrin MnTnHex-2-PyP5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for ... Full text Link to item Cite

Antibiotic Prophylaxis for Megaprosthetic Reconstructions: Drug and Dosing May Matter More than Duration.

Journal Article Antimicrob Agents Chemother · October 18, 2022 In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperat ... Full text Link to item Cite

Genetically Engineered Nanoparticles of Asymmetric Triblock Polypeptide with a Platinum(IV) Cargo Outperforms a Platinum(II) Analog and Free Drug in a Murine Cancer Model.

Journal Article Nano Lett · July 27, 2022 The development of platinum(Pt)-drugs for cancer therapy has stalled, as no new Pt-drugs have been approved in over a decade. Packaging small molecule drugs into nanoparticles is a way to enhance their therapeutic efficacy. To date, there has been no direc ... Full text Link to item Cite

Manganese Porphyrin Promotes Post Cardiac Arrest Recovery in Mice and Rats.

Journal Article Biology (Basel) · June 24, 2022 Introduction Cardiac arrest (CA) and resuscitation induces global cerebral ischemia and reperfusion, causing neurologic deficits or death. Manganese porphyrins, superoxide dismutase mimics, are reportedly able to effectively reduce ischemic injury in brain ... Full text Link to item Cite

Prospective clinical trial of disulfiram plus copper in men with metastatic castration-resistant prostate cancer.

Journal Article Prostate · May 2022 BACKGROUND: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC u ... Full text Link to item Cite

HSP90-Specific nIR Probe Identifies Aggressive Prostate Cancers: Translation from Preclinical Models to a Human Phase I Study.

Journal Article Mol Cancer Ther · January 2022 A noninvasive test to discriminate indolent prostate cancers from lethal ones would focus treatment where necessary while reducing overtreatment. We exploited the known activity of heat shock protein 90 (Hsp90) as a chaperone critical for the function of n ... Full text Link to item Cite

Safety Profile of Rapamycin Perfluorocarbon Nanoparticles for Preventing Cisplatin-Induced Kidney Injury.

Journal Article Nanomaterials (Basel, Switzerland) · January 2022 Cancer treatment-induced toxicities may restrict maximal effective dosing for treatment and cancer survivors' quality of life. It is critical to develop novel strategies that mitigate treatment-induced toxicity without affecting the efficacy of anti-cancer ... Full text Cite

A Redox-active Mn Porphyrin, MnTnBuOE-2-PyP5+, Synergizes with Carboplatin in Treatment of Chemoresistant Ovarian Cell Line.

Journal Article Oxid Med Cell Longev · 2022 We have employed a redox-active MnP (MnTnBuOE-2-PyP5+, Mn(III) meso-tetrakis (N-n-butoxyethylpyridinium-2-yl) porphyrin) frequently identified as superoxide dismutase mimic or BMX-001, to explore the redox status of normal ovarian cell in relation to two o ... Full text Link to item Cite

Measuring Nonapoptotic Caspase Activity with a Transgenic Reporter in Mice.

Journal Article eNeuro · 2022 The protease caspase-3 is a key mediator of apoptotic programmed cell death. But weak or transient caspase activity can contribute to neuronal differentiation, axonal pathfinding, and synaptic long-term depression. Despite the importance of sublethal, or n ... Full text Link to item Cite

ENTPD1 (CD39) Expression Inhibits UVR-Induced DNA Damage Repair through Purinergic Signaling and Is Associated with Metastasis in Human Cutaneous Squamous Cell Carcinoma.

Journal Article J Invest Dermatol · October 2021 UVR and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells promote cSCC carcinogenesis, and in other solid tumors, infiltrating regulatory T cells and CD8+ T cells express ectonucleoside triphosphate d ... Full text Link to item Cite

A Pilot Study of Associations Between Visceral Fat, IL-6, and Urinary F2-Isoprostanes in Older Adults Exposed to a Diet Intervention.

Journal Article Curr Dev Nutr · June 2021 BACKGROUND: Short-term markers of successful visceral adipose tissue (VAT) loss are needed. Urinary F2-isoprostanes might serve as a marker for intensified lipid metabolism, whereas circulating IL-6 might stimulate fat oxidation and enhance mobilization of ... Full text Link to item Cite

Increasing O-GlcNAcylation is neuroprotective in young and aged brains after ischemic stroke.

Journal Article Exp Neurol · May 2021 Spliced X-box binding protein-1 (XBP1s) together with the hexosamine biosynthetic pathway (HBP) and O-GlcNAcylation forms the XBP1s/HBP/O-GlcNAc axis. Our previous studies have provided evidence that activation of this axis is neuroprotective after ischemi ... Full text Open Access Link to item Cite

Hyperthermia, bladder pressure, and intravesical drug delivery.

Conference Journal of Clinical Oncology · February 20, 2021 469 Background: Little is known about the pharmacokinetics of intravesical chemotherapies. Various parameters can be altered including temperature, dwell time, drug concentration, and bladder pressure. Here, we hypothesize that i ... Full text Cite

Manganese Porphyrin and Radiotherapy Improves Local Tumor Response and Overall Survival in Orthotopic Murine Mammary Carcinoma Models.

Journal Article Radiat Res · February 1, 2021 Novel synthetic compounds, known as manganese porphyrins (MnPs), have been designed to shift the redox status of both normal cells and cancer cells. When MnPs are coupled with cancer therapies, such as radiation, they have been shown to sensitize tumor cel ... Full text Link to item Cite

H2O2-Driven Anticancer Activity of Mn Porphyrins and the Underlying Molecular Pathways.

Journal Article Oxid Med Cell Longev · 2021 Mn(III) ortho-N-alkyl- and N-alkoxyalkyl porphyrins (MnPs) were initially developed as superoxide dismutase (SOD) mimics. These compounds were later shown to react with numerous reactive species (such as ONOO-, H2O2, H2S, CO3 •-, ascorbate, and GSH). Moreo ... Full text Open Access Link to item Cite

MnTnBuOE-2-PyP5+ Ascorbate in the Treatment of Ovarian Cancer

Conference Free Radical Biology and Medicine · November 2020 Full text Cite

Preclinical Testing of a Novel Niclosamide Stearate Prodrug Therapeutic (NSPT) Shows Efficacy Against Osteosarcoma.

Journal Article Mol Cancer Ther · July 2020 Therapeutic advances for osteosarcoma have stagnated over the past several decades, leading to an unmet clinical need for patients. The purpose of this study was to develop a novel therapy for osteosarcoma by reformulating and validating niclosamide, an es ... Full text Open Access Link to item Cite

Efficacy of osimertinib against EGFRvIII+ glioblastoma.

Journal Article Oncotarget · June 2, 2020 Epidermal Growth Factor Receptor variant III (EGFRvIII) is an active mutant form of EGFR that drives tumor growth in a subset of glioblastoma (GBM). It occurs in over 20% of GBMs, making it a promising receptor for small molecule targeted therapy. We hypot ... Full text Link to item Cite

Fe Porphyrin-Based SOD Mimic and Redox-Active Compound, (OH)FeTnHex-2-PyP4+, in a Rodent Ischemic Stroke (MCAO) Model: Efficacy and Pharmacokinetics as Compared to Its Mn Analogue, (H2O)MnTnHex-2-PyP5+.

Journal Article Antioxidants (Basel) · June 1, 2020 Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin, (H2O)MnTnHex-2-PyP5+ (MnHex) carrying long hexyl chains, is a lipophilic mimic of superoxide dismutase (SOD) and a redox-active drug candidate. MnHex crosses the blood-brain barrier, and improved ne ... Full text Open Access Link to item Cite

Surface Contamination With Antineoplastic Drugs on Two Inpatient Oncology Units.

Journal Article Oncol Nurs Forum · May 1, 2020 OBJECTIVES: To measure surface contamination with antineoplastic drugs on inpatient oncology units and to characterize nursing staff personal protective equipment (PPE) use and factors that predict this use. SAMPLE & SETTING: A descriptive pilot study ... Full text Link to item Cite

Genetically Encoded Stealth Nanoparticles of a Zwitterionic Polypeptide-Paclitaxel Conjugate Have a Wider Therapeutic Window than Abraxane in Multiple Tumor Models.

Journal Article Nano Lett · April 8, 2020 Small-molecule therapeutics demonstrate suboptimal pharmacokinetics and bioavailability due to their hydrophobicity and size. One way to overcome these limitations-and improve their efficacy-is to use "stealth" macromolecular carriers that evade uptake by ... Full text Link to item Cite

First in human dose calculation of a single-chain bispecific antibody targeting glioma using the MABEL approach.

Journal Article J Immunother Cancer · April 2020 BACKGROUND: First-in-human (FIH) clinical trials require careful selection of a safe yet biologically relevant starting dose. Typically, such starting doses are selected based on toxicity studies in a pharmacologically relevant animal model. However, with ... Full text Link to item Cite

Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study.

Journal Article Int J Hyperthermia · 2020 BACKGROUND: Hyperthermia (heating to 43 °C) activates the innate immune system and improves bladder cancer chemosensitivity. OBJECTIVE: To evaluate the tissue penetration and safety of convective hyperthermia combined with intravesical mitomycin C (MMC) ph ... Full text Open Access Link to item Cite

Hyperthermia Improves Solubility of Intravesical Chemotherapeutic Agents.

Journal Article Bladder Cancer · 2020 BACKGROUND: Nearly 70% of all new cases of bladder cancer are non-muscle invasive disease, the treatment for which includes transurethral resection followed by intravesical therapy. Unfortunately, recurrence rates approach 50% in part due to poor intravesi ... Full text Open Access Link to item Cite

25 years of development of Mn porphyrins - from mimics of superoxide dismutase enzymes to thiol signaling to clinical trials: The story of our life in the USA

Chapter · January 1, 2020 We have developed Mn porphyrins (MnPs) initially as mimics of superoxide dismutase (SOD) enzymes based on structure-activity relationships. Several cationic Mn porphyrins, being substituted with cationic ortho N-alkyl- or alkoxyalkylpyridyl groups in meso ... Full text Cite

25 years of development of Mn porphyrins-from mimics of superoxide dismutase enzymes to thiol signaling to clinical trials: The story of our life in the USA

Journal Article Journal of Porphyrins and Phthalocyanines · November 1, 2019 We have developed Mn porphyrins (MnPs) initially as mimics of superoxide dismutase (SOD) enzymes based on structure-activity relationships. Several cationic Mn porphyrins, being substituted with cationic ortho N-alkyl-or alkoxyalkylpyridyl groups in meso p ... Full text Cite

CRISPR Editing of Mutant IDH1 R132H Induces a CpG Methylation-Low State in Patient-Derived Glioma Models of G-CIMP.

Journal Article Mol Cancer Res · October 2019 Mutations in isocitrate dehydrogenases 1 and 2 (IDH) occur in the majority of World Health Organization grade II and III gliomas. IDH1/2 active site mutations confer a neomorphic enzyme activity producing the oncometabolite D-2-hydroxyglutarate (D-2HG), wh ... Full text Link to item Cite

Pharmacokinetic Analysis of a Novel Human EGFRvIII:CD3 Bispecific Antibody in Plasma and Whole Blood Using a High-Resolution Targeted Mass Spectrometry Approach.

Journal Article J Proteome Res · August 2, 2019 Bispecific single chain antibody fragments (bi-scFv) represent an emerging class of biotherapeutics. We recently developed a fully human bi-scFv (EGFRvIII:CD3 bi-scFv) with the goal of redirecting CD3-expressing T cells to recognize and destroy malignant, ... Full text Link to item Cite

Disrupting the vicious cycle created by NOX activation in sickle erythrocytes exposed to hypoxia/reoxygenation prevents adhesion and vasoocclusion.

Journal Article Redox Biol · July 2019 In sickle cell disease (SCD), recurrent painful vasoocclusive crisis are likely caused by repeated episodes of hypoxia and reoxygenation. The sickle erythrocyte (SSRBC) adhesion plays an active role in vasoocclusion. However, the effect of prolonged reoxyg ... Full text Open Access Link to item Cite

MTAP Loss Promotes Stemness in Glioblastoma and Confers Unique Susceptibility to Purine Starvation.

Journal Article Cancer Res · July 1, 2019 Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic ... Full text Link to item Cite

Mn Porphyrin-Based Redox-Active Drugs: Differential Effects as Cancer Therapeutics and Protectors of Normal Tissue Against Oxidative Injury.

Journal Article Antioxid Redox Signal · December 1, 2018 SIGNIFICANCE: After approximatelty three decades of research, two Mn(III) porphyrins (MnPs), MnTE-2-PyP5+ (BMX-010, AEOL10113) and MnTnBuOE-2-PyP5+ (BMX-001), have progressed to five clinical trials. In parallel, another similarly potent metal-based supero ... Full text Link to item Cite

ACTR-28. PHASE 1 DOSE ESCALATION TRIAL OF THE SAFETY OF BMX-001 CONCURRENT WITH RADIATION THERAPY AND TEMOZOLOMIDE IN NEWLY DIAGNOSED PATIENTS WITH HIGH-GRADE GLIOMAS

Conference Neuro-Oncology · November 5, 2018 BACKGROUND BMX-001 (MnTnBuOE-2-PyP5+) is a metalloporphyrin with differential action in response to oxidative stress caused by radiation therapy (RT)and chemotherapy, both critical components in the treatment of high-grade gliomas (HGG). In preclinical stu ... Full text Link to item Cite

Radiation-Mediated Tumor Growth Inhibition Is Significantly Enhanced with Redox-Active Compounds That Cycle with Ascorbate.

Journal Article Antioxid Redox Signal · November 1, 2018 AIMS: We aim here to demonstrate that radiation (RT) enhances tumor sensitization by only those Mn complexes that are redox active and cycle with ascorbate (Asc), thereby producing H2O2 and utilizing it subsequently in protein S-glutathionylation in a glut ... Full text Link to item Cite

Identification of DK419, a potent inhibitor of Wnt/β-catenin signaling and colorectal cancer growth.

Journal Article Bioorg Med Chem · November 1, 2018 The Wnt signaling pathway is critical for normal tissue development and is an underlying mechanism of disease when dysregulated. Previously, we reported that the drug Niclosamide inhibits Wnt/β-catenin signaling by decreasing the cytosolic levels of Dishev ... Full text Link to item Cite

Mn porphyrin/ascorbate sensitizes serous epithelial ovarian cancer to chemotherapy

Conference Free Radical Biology and Medicine · November 2018 Full text Cite

Enhanced Drug Delivery to the Skin Using Liposomes.

Journal Article Plast Reconstr Surg Glob Open · July 2018 BACKGROUND: Enhancing drug delivery to the skin has importance in many therapeutic strategies. In particular, the outcome in vascularized composite allotransplantation mainly depends on systemic immunosuppression to prevent and treat episodes of transplant ... Full text Open Access Link to item Cite

Abstract 1805: Development of a selective androgen receptor degrader (SARD) for treatment of castration-resistant prostate cancer

Conference Cancer Research · July 1, 2018 AbstractCurrent treatments for prostate cancer are centered on blocking androgen-signaling axis, which is the target of several clinical androgen receptor (AR) antagonists such as enzalutamide. Recent studie ... Full text Cite

Effects of 2 years of caloric restriction on oxidative status assessed by urinary F2-isoprostanes: The CALERIE 2 randomized clinical trial.

Journal Article Aging Cell · April 2018 Calorie restriction (CR) without malnutrition slows aging in animal models. Oxidative stress reduction was proposed to mediate CR effects. CR effect on urinary F2-isoprostanes, validated oxidative stress markers, was assessed in CALERIE, a two-year randomi ... Full text Link to item Cite

Post-Irradiation Treatment with a Superoxide Dismutase Mimic, MnTnHex-2-PyP5+, Mitigates Radiation Injury in the Lungs of Non-Human Primates after Whole-Thorax Exposure to Ionizing Radiation.

Journal Article Antioxidants (Basel) · March 7, 2018 Radiation injury to the lung is the result of acute and chronic free radical formation, and there are currently few effective means of mitigating such injury. Studies in rodents indicate that superoxide dismutase mimetics may be effective in this regard; h ... Full text Link to item Cite

Adaptive Evolution of the GDH2 Allosteric Domain Promotes Gliomagenesis by Resolving IDH1R132H-Induced Metabolic Liabilities.

Journal Article Cancer Res · January 1, 2018 Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malign ... Full text Link to item Cite

A Testosterone Metabolite 19-Hydroxyandrostenedione Induces Neuroendocrine Trans-Differentiation of Prostate Cancer Cells via an Ectopic Olfactory Receptor.

Journal Article Front Oncol · 2018 Olfactory receptor OR51E2, also known as a Prostate Specific G-Protein Receptor, is highly expressed in prostate cancer but its function is not well understood. Through in silico and in vitro analyses, we identified 24 agonists and 1 antagonist for this re ... Full text Open Access Link to item Cite

Protection Of Neurocognitive Function During Cranial Irradiation Of Brain Tumors

Conference Free Radical Biology and Medicine · November 2017 Full text Cite

Niclosamide-conjugated polypeptide nanoparticles inhibit Wnt signaling and colon cancer growth.

Journal Article Nanoscale · August 31, 2017 Abnormal Wnt activity is a major mechanism responsible for many diseases, including cancer. Previously, we reported that the anthelmintic drug Niclosamide (NIC) inhibits Wnt/β-catenin signaling and suppresses colon cancer cell growth. Although the pharmaco ... Full text Link to item Cite

Discovery of a selective androgen receptor degrader (SARD) for treatment of castration-resistant prostate cancer

Conference ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY · August 20, 2017 Link to item Cite

CNS bioavailability and radiation protection of normal hippocampal neurogenesis by a lipophilic Mn porphyrin-based superoxide dismutase mimic, MnTnBuOE-2-PyP5.

Journal Article Redox Biol · August 2017 Although radiation therapy can be effective against cancer, potential damage to normal tissues limits the amount that can be safely administered. In central nervous system (CNS), radiation damage to normal tissues is presented, in part, as suppressed hippo ... Full text Link to item Cite

Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy.

Journal Article Cancer Chemother Pharmacol · August 2017 PURPOSE: Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokineti ... Full text Link to item Cite

Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling.

Journal Article Oncogene · July 27, 2017 Despite the advances in the diagnosis and treatment of breast cancer, breast cancers still cause significant mortality. For some patients, especially those with triple-negative breast cancer, current treatments continue to be limited and ineffective. There ... Full text Link to item Cite

Cystine addiction of triple-negative breast cancer associated with EMT augmented death signaling.

Journal Article Oncogene · July 27, 2017 This corrects the article DOI: 10.1038/onc.2016.394. ... Full text Link to item Cite

Inhibition of the Continuum of Radiation-Induced Normal Tissue Injury by a Redox-Active Mn Porphyrin.

Journal Article Radiat Res · July 2017 Normal tissue damage after head and neck radiotherapy involves a continuum of pathologic events to the mucosa, tongue and salivary glands. We examined the radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three stages of normal tiss ... Full text Link to item Cite

A phase I study of perifosine with temsirolimus for recurrent pediatric solid tumors.

Conference Pediatr Blood Cancer · July 2017 BACKGROUND: The PI3K/AKT/mTOR pathway is aberrantly activated in many pediatric solid tumors including gliomas and medulloblastomas. Preclinical data in a pediatric glioma model demonstrated that the combination of perifosine (AKT inhibitor) and temsirolim ... Full text Link to item Cite

A phase i study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors

Conference PLoS ONE · June 1, 2017 The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label d ... Full text Cite

Urinary F2-isoprostanes and the risk of hypertension.

Journal Article Ann Epidemiol · June 2017 PURPOSE: There is strong biological plausibility for a causal role of reactive oxygen species in vascular pathology but no direct epidemiological evidence linking elevated reactive oxygen species levels to hypertension development. We examined cross-sectio ... Full text Link to item Cite

Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression.

Journal Article Mol Cancer Res · May 2017 IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population a ... Full text Link to item Cite

Challenges encountered during development of Mn porphyrin-based, potent redox-active drug and superoxide dismutase mimic, MnTnBuOE-2-PyP5+, and its alkoxyalkyl analogues.

Journal Article J Inorg Biochem · April 2017 We disclose here the studies that preceded and guided the preparation of the metal-based, redox-active therapeutic Mn(III) meso-tetrakis(N-n-butoxyethylpyridyl)porphyrin, MnTnBuOE-2-PyP5+ (BMX-001), which is currently in Phase I/II Clinical Trials at Duke ... Full text Open Access Link to item Cite

A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors.

Journal Article PLoS One · 2017 The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label d ... Full text Link to item Cite

Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer.

Journal Article Nat Chem Biol · October 2016 Clinical resistance to the second-generation antiandrogen enzalutamide in castration-resistant prostate cancer (CRPC), despite persistent androgen receptor (AR) activity in tumors, highlights an unmet medical need for next-generation antagonists. We have i ... Full text Link to item Cite

Hypo-CpG methylation controls PTEN expression and cell apoptosis in irradiated lung.

Journal Article Free Radic Res · August 2016 PURPOSE: The current study was designed to address our hypothesis that oxidative stress secondary to the ionizing event upregulates phosphatase and tensin homolog (PTEN) mRNA and protein in the lungs of C57BL/6J mice through oxidative DNA damage resulting ... Full text Link to item Cite

SSRI Augmentation by 5-Hydroxytryptophan Slow Release: Mouse Pharmacodynamic Proof of Concept.

Journal Article Neuropsychopharmacology · August 2016 Drugs, notably SSRIs, that elevate brain extracellular 5-HT (5-HTExt) are antidepressants. Unfortunately, most patients fail to remit. Multipronged clinical evidence suggests that elevating 5-HTExt beyond the SSRI effect enhances antidepressant efficacy, b ... Full text Link to item Cite

Nonclinical Safety and Toxicokinetics of MnTnBuOE-2-PyP5+ (BMX-001).

Conference Int J Toxicol · July 2016 BMX-001, a manganese porphyrin that has anti-inflammatory, antioxidant, and antitumor properties, is being developed as a potential therapeutic for high-grade glioma (HGG) and head and neck (H&N) cancer. An IND has been opened for BMX-001 in the treatment ... Full text Link to item Cite

Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain.

Journal Article Sci Rep · June 1, 2016 TRPV4 ion channels represent osmo-mechano-TRP channels with pleiotropic function and wide-spread expression. One of the critical functions of TRPV4 in this spectrum is its involvement in pain and inflammation. However, few small-molecule inhibitors of TRPV ... Full text Open Access Link to item Cite

Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.

Journal Article Environ Mol Mutagen · June 2016 Combinations of radiotherapy (RT) and chemotherapy have shown efficacy toward brain tumors. However, therapy-induced oxidative stress can damage normal brain tissue, resulting in both progressive neurocognitive loss and diminished quality of life. We have ... Full text Link to item Cite

Opinion on Schmidt et al.

Journal Article Antioxid Redox Signal · March 20, 2016 Full text Link to item Cite

A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer.

Journal Article Sci Transl Med · January 6, 2016 Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, a ... Full text Link to item Cite

Anticancer therapeutic potential of Mn porphyrin/ascorbate system.

Journal Article Free Radic Biol Med · December 2015 Ascorbate (Asc) as a single agent suppressed growth of several tumor cell lines in a mouse model. It has been tested in a Phase I Clinical Trial on pancreatic cancer patients where it exhibited no toxicity to normal tissue yet was of only marginal efficacy ... Full text Link to item Cite

Novel Manganese-Porphyrin Superoxide Dismutase-Mimetic Widens the Therapeutic Margin in a Preclinical Head and Neck Cancer Model.

Journal Article Int J Radiat Oncol Biol Phys · November 15, 2015 PURPOSE: To test the effects of a novel Mn porphyrin oxidative stress modifier, Mn(III) meso-tetrakis(N-n-butoxyethylpyridinium-2-yl)porphyrin (MnBuOE), for its radioprotective and radiosensitizing properties in normal tissue versus tumor, respectively. ME ... Full text Open Access Link to item Cite

A comprehensive evaluation of catalase-like activity of different classes of redox-active therapeutics.

Journal Article Free Radic Biol Med · September 2015 Because of the increased insight into the biological role of hydrogen peroxide (H2O2) under physiological and pathological conditions and the role it presumably plays in the action of natural and synthetic redox-active drugs, there is a need to accurately ... Full text Link to item Cite

Structure-activity studies of Wnt/β-catenin inhibition in the Niclosamide chemotype: Identification of derivatives with improved drug exposure.

Journal Article Bioorg Med Chem · September 1, 2015 The Wnt signaling pathway plays a key role in regulation of organ development and tissue homeostasis. Dysregulated Wnt activity is one of the major underlying mechanisms responsible for many diseases including cancer. We previously reported the FDA-approve ... Full text Link to item Cite

A paclitaxel-loaded recombinant polypeptide nanoparticle outperforms Abraxane in multiple murine cancer models.

Journal Article Nat Commun · August 4, 2015 Packaging clinically relevant hydrophobic drugs into a self-assembled nanoparticle can improve their aqueous solubility, plasma half-life, tumour-specific uptake and therapeutic potential. To this end, here we conjugated paclitaxel (PTX) to recombinant chi ... Full text Link to item Cite

An educational overview of the chemistry, biochemistry and therapeutic aspects of Mn porphyrins--From superoxide dismutation to H2O2-driven pathways.

Journal Article Redox Biol · August 2015 Most of the SOD mimics thus far developed belong to the classes of Mn-(MnPs) and Fe porphyrins(FePs), Mn(III) salens, Mn(II) cyclic polyamines and metal salts. Due to their remarkable stability we have predominantly explored Mn porphyrins, aiming initially ... Full text Link to item Cite

Abstract SY36-03: Intraoperative molecular imaging with protease-activated fluorescent imaging agents

Conference Cancer Research · August 1, 2015 AbstractIntra-operative detection of residual cancer in the tumor bed can be used to decrease the risk of a positive surgical margin, reduce the rate of re-excision, and tailor adjuvant therapy. LUM015 is a ... Full text Cite

Antineoplastic drug exposure in an ambulatory setting: a pilot study.

Journal Article Cancer Nurs · 2015 BACKGROUND: Exposure to antineoplastic drugs confers health risks to workers, yet little is known about the exposure after a drug spill, nor has the relationship between exposure and organizational factors such as staffing and work environment been studied ... Full text Link to item Cite

Radioprotection of the brain white matter by Mn(III) n-Butoxyethylpyridylporphyrin-based superoxide dismutase mimic MnTnBuOE-2-PyP5+.

Journal Article Mol Cancer Ther · January 2015 Cranial irradiation is a standard therapy for primary and metastatic brain tumors. A major drawback of radiotherapy (RT), however, is long-term cognitive loss that affects quality of life. Radiation-induced oxidative stress in normal brain tissue is though ... Full text Link to item Cite

A high-throughput in vitro drug screen in a genetically engineered mouse model of diffuse intrinsic pontine glioma identifies BMS-754807 as a promising therapeutic agent.

Journal Article PLoS One · 2015 Diffuse intrinsic pontine gliomas (DIPGs) represent a particularly lethal type of pediatric brain cancer with no effective therapeutic options. Our laboratory has previously reported the development of genetically engineered DIPG mouse models using the RCA ... Full text Open Access Link to item Cite

Urinary F2-isoprostanes and metabolic markers of fat oxidation.

Journal Article Oxid Med Cell Longev · 2015 Metabolomic studies of increased fat oxidation showed increase in circulating acylcarnitines C2, C8, C10, and C12 and decrease in C3, C4, and C5. We hypothesize that urinary F2-isoprostanes reflect intensity of fatty acid oxidation and are associated with ... Full text Link to item Cite

Rational design of superoxide dismutase (SOD) mimics: the evaluation of the therapeutic potential of new cationic Mn porphyrins with linear and cyclic substituents.

Journal Article Inorg Chem · November 3, 2014 Our goal herein has been to gain further insight into the parameters which control porphyrin therapeutic potential. Mn porphyrins (MnTnOct-2-PyP(5+), MnTnHexOE-2-PyP(5+), MnTE-2-PyPhP(5+), and MnTPhE-2-PyP(5+)) that bear the same positive charge and same n ... Full text Link to item Cite

Novel amphiphilic cationic porphyrin and its Ag(II) complex as potential anticancer agents.

Journal Article J Inorg Biochem · November 2014 In the present study we have synthesized a novel amphiphilic porphyrin and its Ag(II) complex through modification of water-soluble porphyrinic structure in order to increase its lipophilicity and in turn pharmacological potency. New cationic non-symmetric ... Full text Link to item Cite

Mitigation of Radiation-Mediated Suppression of Hippocampal Neurogenesis

Journal Article Free Radical Biology and Medicine · November 2014 Full text Cite

Rational Design of New Cationic Mn Porphyrins and Evaluation of Their Therapeutic Potential

Journal Article Free Radical Biology and Medicine · November 2014 Full text Cite

Abstract 3774: Hyperthermia treatment overcomes temozolomide resistance in glioma cells by downregulating MGMT expression and increasing temozolomide uptake

Conference Cancer Research · October 1, 2014 AbstractGlioblastoma multiforme (GBM) is the most common and malignant brain tumor. Current standard treatment for GBM following maximum safe resection includes temozolomide (TMZ) with concurrent radiotherap ... Full text Cite

Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia.

Journal Article J Biol Chem · August 22, 2014 Mutations in the cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations targe ... Full text Link to item Cite

A joint analysis of metabolomics and genetics of breast cancer.

Journal Article Breast Cancer Res · August 5, 2014 INTRODUCTION: Remodeling of cellular metabolism appears to be a consequence and possibly a cause of oncogenic transformation in human cancers. Specific aspects of altered tumor metabolism may be amenable to therapeutic intervention and could be coordinated ... Full text Link to item Cite

Complex chemistry and biology of redox-active compounds, commonly known as SOD mimics, affect their therapeutic effects.

Journal Article Antioxid Redox Signal · May 20, 2014 This Editorial has the intention to stress the complex chemistry and biology of redox-active compounds, regarded as SOD mimics. It further aims to caution the researchers of the importance of being up-to-date with the present knowledge on such compounds an ... Full text Link to item Cite

Manganese-based superoxide dismutase mimics modify both acute and long-term outcome severity in a Drosophila melanogaster model of classic galactosemia.

Journal Article Antioxid Redox Signal · May 20, 2014 AIMS: The goal of this study was to use two manganese (Mn)-based superoxide dismutase (SOD) mimics to test the hypothesis that reactive oxygen species contribute to both acute and long-term outcomes in a galactose-1P uridylyltransferase (GALT)-null Drosoph ... Full text Link to item Cite

SOD therapeutics: latest insights into their structure-activity relationships and impact on the cellular redox-based signaling pathways.

Journal Article Antioxid Redox Signal · May 20, 2014 SIGNIFICANCE: Superoxide dismutase (SOD) enzymes are indispensable and ubiquitous antioxidant defenses maintaining the steady-state levels of O2·(-); no wonder, thus, that their mimics are remarkably efficacious in essentially any animal model of oxidative ... Full text Link to item Cite

Differential localization and potency of manganese porphyrin superoxide dismutase-mimicking compounds in Saccharomyces cerevisiae.

Journal Article Redox Biol · 2014 Cationic Mn(III) porphyrin complexes based on MnTM-2-PyP are among the most promising superoxide dismutase (SOD) mimicking compounds being considered as potential anti-inflammatory drugs. We studied four of these active compounds in the yeast Saccharomyces ... Full text Link to item Cite

The complex mechanistic aspects of redox-active compounds, commonly regarded as SOD mimics

Journal Article BioInorganic Reaction Mechanisms · December 1, 2013 This review aims to clarify (1) what is a true mimic of superoxide dismutase family of enzymes, SOD; and (2) whether such compound could act as SOD mimic in a complex biological milieu. Several groups of compounds (metalloporphyrins, metallocorroles, Mn bi ... Full text Cite

Differential coordination demands in Fe versus Mn water-soluble cationic metalloporphyrins translate into remarkably different aqueous redox chemistry and biology.

Journal Article Inorg Chem · May 20, 2013 The different biological behavior of cationic Fe and Mn pyridylporphyrins in Escherichia coli and mouse studies prompted us to revisit and compare their chemistry. For that purpose, the series of ortho and meta isomers of Fe(III) meso-tetrakis-N-alkylpyrid ... Full text Open Access Link to item Cite

Comprehensive pharmacokinetic studies and oral bioavailability of two Mn porphyrin-based SOD mimics, MnTE-2-PyP5+ and MnTnHex-2-PyP5+.

Journal Article Free Radic Biol Med · May 2013 The cationic, ortho Mn(III) N-alkylpyridylporphyrins (alkyl=ethyl, E, and n-hexyl, nHex) MnTE-2-PyP(5+) (AEOL10113, FBC-007) and MnTnHex-2-PyP(5+) have proven efficacious in numerous in vivo animal models of diseases having oxidative stress in common. The ... Full text Open Access Link to item Cite

Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas.

Journal Article Cancer Res · January 15, 2013 Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually a ... Full text Open Access Link to item Cite

Design, mechanism of action, bioavailability and therapeutic effects of mn porphyrin-based redox modulators.

Journal Article Med Princ Pract · 2013 Based on aqueous redox chemistry and simple in vivo models of oxidative stress, Escherichia coli and Saccharomyces cerevisiae, the cationic Mn(III) N-substituted pyridylporphyrins (MnPs) have been identified as the most potent cellular redox modulators wit ... Full text Open Access Link to item Cite

Enzyme redesign guided by cancer-derived IDH1 mutations.

Journal Article Nat Chem Biol · November 2012 Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that cataly ... Full text Link to item Cite

Urinary biomarkers of oxidative status.

Journal Article Clin Chim Acta · October 9, 2012 Oxidative damage produced by reactive oxygen species (ROS) has been implicated in the etiology and pathology of many health conditions, including a large number of chronic diseases. Urinary biomarkers of oxidative status present a great opportunity to stud ... Full text Link to item Cite

Racial differences in urinary F2-isoprostane levels and the cross-sectional association with BMI.

Journal Article Obesity (Silver Spring) · October 2012 Levels of four urinary F(2)-isoprostanes (F(2)-IsoPs) were examined in a large sample of the Insulin Resistance Atherosclerosis Study (IRAS) multiethnic cohort: 237 African Americans (AAs), 342 non-Hispanic whites (NHWs), and 275 Hispanic whites (HWs). F(2 ... Full text Link to item Cite

Endogenous production of extracellular adenosine by trabecular meshwork cells: potential role in outflow regulation.

Journal Article Invest Ophthalmol Vis Sci · October 1, 2012 PURPOSE: To investigate the mechanisms for endogenous production of extracellular adenosine in trabecular meshwork (TM) cells and evaluate its physiological relevance to the regulation of aqueous humor outflow facility. METHODS: Extra-cellular levels of ad ... Full text Link to item Cite

Urinary F2-isoprostanes, obesity, and weight gain in the IRAS cohort.

Journal Article Obesity (Silver Spring) · September 2012 Obesity has been associated with increased F(2)-isoprostane (F(2)-IsoP) levels cross-sectionally. However, the prospective association may be inverse, based on our earlier finding that elevated urinary F(2)-IsoP levels predict lower risk of diabetes. This ... Full text Link to item Cite

Systemic markers of oxidative status and colorectal adenomatous polyps.

Journal Article Ann Epidemiol · August 2012 PURPOSE: Oxidative damage has been implicated in carcinogenesis. We hypothesized that elevated systemic oxidative status would be associated with later occurrence of colorectal adenomatous polyps, a precursor of colorectal cancer. METHODS: We examined the ... Full text Link to item Cite

Mutant IDH1 is required for IDH1 mutated tumor cell growth.

Journal Article Oncotarget · August 2012 Frequent somatic hotspot mutations in isocitrate dehydrogenase 1 (IDH1) have been identified in gliomas, acute myeloid leukemias, chondrosarcomas, and other cancers, providing a likely avenue for targeted cancer therapy. However, whether mutant IDH1 protei ... Full text Open Access Link to item Cite

A new SOD mimic, Mn(III) ortho N-butoxyethylpyridylporphyrin, combines superb potency and lipophilicity with low toxicity.

Journal Article Free Radic Biol Med · May 1, 2012 The Mn porphyrins of k(cat)(O(2)(.-)) as high as that of a superoxide dismutase enzyme and of optimized lipophilicity have already been synthesized. Their exceptional in vivo potency is at least in part due to their ability to mimic the site and location o ... Full text Open Access Link to item Cite

Manganese superoxide dismutase, MnSOD and its mimics.

Journal Article Biochim Biophys Acta · May 2012 Increased understanding of the role of mitochondria under physiological and pathological conditions parallels increased exploration of synthetic and natural compounds able to mimic MnSOD - endogenous mitochondrial antioxidant defense essential for the exis ... Full text Link to item Cite

The effect of aprepitant and race on the pharmacokinetics of cyclophosphamide in breast cancer patients.

Journal Article Cancer Chemother Pharmacol · May 2012 PURPOSE: The prodrug cyclophosphamide is metabolized by cytochrome P450(CYP)2B6 to the active metabolite, 4-hydroxycyclophosphamide (4-OH), and by CYP3A4/5 to toxic chloracetaldehyde and 2-dechloroethylcyclophosphamide (DCE). Since aprepitant is a moderate ... Full text Link to item Cite

Abstract 4766: The use of deuterium isotope effects to shift the partitioning of cyclophosphamide and ifosfamide among competing, P450-dependent, oxidative pathways

Conference Cancer Research · April 15, 2012 AbstractProdrugs cyclophosphamide and ifosfamide are each ‘activated’ through a P450 oxidation at the C-4 position of the oxazaphosphorine ring. This reaction triggers a series of spontaneous (non-enzymatic) ... Full text Cite

Sampling and mass spectrometric analytical methods for five antineoplastic drugs in the healthcare environment.

Journal Article J Oncol Pharm Pract · March 2012 CONTEXT: Healthcare worker exposure to antineoplastic drugs continues to be reported despite safe handling guidelines published by several groups. Sensitive sampling and analytical methods are needed so that occupational safety and health professionals may ... Full text Link to item Cite

Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes.

Journal Article Diabetes Care · January 2012 OBJECTIVE: We have previously reported evidence of an inverse association between a urinary F(2)-isoprostane and type 2 diabetes risk in a pilot case-control study nested within the Insulin Resistance Atherosclerosis Study (IRAS). Here, we report the resul ... Full text Link to item Cite

Design of Mn porphyrins for treating oxidative stress injuries and their redox-based regulation of cellular transcriptional activities.

Journal Article Amino Acids · January 2012 The most efficacious Mn(III) porphyrinic (MnPs) scavengers of reactive species have positive charges close to the Mn site, whereby they afford thermodynamic and electrostatic facilitation for the reaction with negatively charged species such as O (2) (•-) ... Full text Link to item Cite

The antioxidant, MnTE-2-PyP, prevents side-effects incurred by prostate cancer irradiation.

Journal Article PLoS One · 2012 Prostate cancer is the most commonly diagnosed cancer, with an estimated 240,000 new cases reported annually in the United States. Due to early detection and advances in therapies, more than 90% of patients will survive 10 years post diagnosis and treatmen ... Full text Link to item Cite

Cytotoxic effects of Mn(III) N-alkylpyridylporphyrins in the presence of cellular reductant, ascorbate.

Journal Article Free Radic Res · November 2011 Due to the ability to easily accept and donate electrons Mn(III)N-alkylpyridylporphyrins (MnPs) can dismute O(2)(·-), reduce peroxynitrite, but also generate reactive species and behave as pro-oxidants if conditions favour such action. Herein two ortho iso ... Full text Link to item Cite

Manganese porphyrin reduces retinal injury induced by ocular hypertension in rats.

Journal Article Exp Eye Res · October 2011 This study aimed to clarify the possible therapeutic benefit of preferential nitric oxide synthase (NOS) inhibition and catalytic antioxidant Mn (III) meso-tetrakis (N-n-hexylpyridinium-2-yl) porphyrin (MnTnHex-2-PyP(5+)) treatment in a rat model of elevat ... Full text Link to item Cite

Neuroprotective efficacy from a lipophilic redox-modulating Mn(III) N-Hexylpyridylporphyrin, MnTnHex-2-PyP: rodent models of ischemic stroke and subarachnoid hemorrhage.

Journal Article J Pharmacol Exp Ther · September 2011 Intracerebroventricular treatment with redox-regulating Mn(III) N-hexylpyridylporphyrin (MnPorphyrin) is remarkably efficacious in experimental central nervous system (CNS) injury. Clinical development has been arrested because of poor blood-brain barrier ... Full text Open Access Link to item Cite

Diverse functions of cationic Mn(III) N-substituted pyridylporphyrins, recognized as SOD mimics.

Journal Article Free Radic Biol Med · September 1, 2011 Oxidative stress, a redox imbalance between the endogenous reactive species and antioxidant systems, is common to numerous pathological conditions such as cancer, central nervous system injuries, radiation injury, diabetes etc. Therefore, compounds able to ... Full text Link to item Cite

Antihelminth compound niclosamide downregulates Wnt signaling and elicits antitumor responses in tumors with activating APC mutations.

Journal Article Cancer Res · June 15, 2011 Wnt/β-catenin pathway activation caused by adenomatous polyposis coli (APC) mutations occurs in approximately 80% of sporadic colorectal cancers (CRC). The antihelminth compound niclosamide downregulates components of the Wnt pathway, specifically Dishevel ... Full text Link to item Cite

Methoxy-derivatization of alkyl chains increases the in vivo efficacy of cationic Mn porphyrins. Synthesis, characterization, SOD-like activity, and SOD-deficient E. coli study of meta Mn(III) N-methoxyalkylpyridylporphyrins.

Journal Article Dalton Trans · April 28, 2011 Cationic Mn(III) N-alkylpyridylporphyrins (MnPs) are potent SOD mimics and peroxynitrite scavengers and diminish oxidative stress in a variety of animal models of central nervous system (CNS) injuries, cancer, radiation, diabetes, etc. Recently, properties ... Full text Open Access Link to item Cite

Effects of aerobic training on oxidative status in postsurgical non-small cell lung cancer patients: a pilot study.

Journal Article Lung cancer (Amsterdam, Netherlands) · April 2011 BackgroundOxidative stress is postulated to contribute to the initiation, promotion, and progression of non-small cell lung cancer (NSCLC). We investigated the effects of supervised, moderate-intensity aerobic training on urinary markers of oxidat ... Full text Cite

Response to Rosenthal et al.

Journal Article Antioxidants and Redox Signaling · March 15, 2011 Full text Cite

Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome.

Journal Article Proc Natl Acad Sci U S A · February 22, 2011 Point mutations of the NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream e ... Full text Link to item Cite

2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP-dependent isocitrate dehydrogenase mutations.

Journal Article PLoS One · February 4, 2011 BACKGROUND: Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2). Several different amino acid substitutions recur at either IDH1 R1 ... Full text Link to item Cite

Bioavailability of metalloporphyrin-based SOD mimics is greatly influenced by a single charge residing on a Mn site.

Journal Article Free Radic Res · February 2011 In the cell Mn porphyrins (MnPs) likely couple with cellular reductants which results in a drop of total charge from 5+ to 4+ and dramatically increases their lipophilicity by up to three orders of magnitude depending upon the length of alkylpyridyl chains ... Full text Link to item Cite

Individual responses to chemotherapy-induced oxidative stress.

Journal Article Breast Cancer Res Treat · January 2011 Differences in redox homeostatic control between cancer patients may underlie predisposition to drug resistance and toxicities. To evaluate interindividual differences in redox response among newly diagnosed breast cancer patients undergoing standard chemo ... Full text Link to item Cite

Superoxide dismutase mimics: chemistry, pharmacology, and therapeutic potential.

Journal Article Antioxid Redox Signal · September 15, 2010 Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidant ... Full text Open Access Link to item Cite

Growth hormone mitigates against lethal irradiation and enhances hematologic and immune recovery in mice and nonhuman primates.

Journal Article PLoS One · June 16, 2010 Medications that can mitigate against radiation injury are limited. In this study, we investigated the ability of recombinant human growth hormone (rhGH) to mitigate against radiation injury in mice and nonhuman primates. BALB/c mice were irradiated with 7 ... Full text Open Access Link to item Cite

Urinary biomarkers of oxidative status in a clinical model of oxidative assault.

Journal Article Cancer Epidemiol Biomarkers Prev · June 2010 BACKGROUND: We used doxorubicin-based chemotherapy as a clinical model of oxidative assault in humans. METHODS: The study recruited newly diagnosed breast cancer patients (n = 23). Urine samples were collected immediately before (T0) and at 1 hour (T1) and ... Full text Link to item Cite

Effect of pazopanib on tumor microenvironment and liposome delivery.

Journal Article Mol Cancer Ther · June 2010 Pathologic angiogenesis creates an abnormal microenvironment in solid tumors, characterized by elevated interstitial fluid pressure (IFP) and hypoxia. Emerging theories suggest that judicious downregulation of proangiogenic signaling pathways may transient ... Full text Link to item Cite

Non-invasive monitoring of intra-tumor drug concentration and therapeutic response using optical spectroscopy.

Journal Article J Control Release · March 19, 2010 Optical spectroscopy was used to monitor changes in tumor physiology with therapy, and its influence on drug delivery and treatment efficacy for hyperthermia treatment combined with free doxorubicin or a low-temperature sensitive liposomal formulation. Mon ... Full text Link to item Cite

Comparative effects of thermosensitive doxorubicin-containing liposomes and hyperthermia in human and murine tumours.

Journal Article Int J Hyperthermia · 2010 PURPOSE: In previous reports, laboratory-made lysolecithin-containing thermosensitive liposome encapsulating doxorubicin (LTSL-DOX) showed potent anticancer effects in FaDu human squamous cell carcinoma. To further study the spectrum of LTSL-DOX activity, ... Full text Link to item Cite

Systemic Markers of Oxidative Status and the Risk of Type 2 Diabetes

Conference Free Radical Biology and Medicine · January 2010 Full text Cite

Manganese Porphyrin Reduces Retinal Injury Induced by Ocular Hypertension

Conference Free Radical Biology and Medicine · January 2010 Full text Cite

High lipophilicity of meta Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase mimics compensates for their lower antioxidant potency and makes them as effective as ortho analogues in protecting superoxide dismutase-deficient Escherichia coli.

Journal Article J Med Chem · December 10, 2009 Lipophilicity/bioavailibility of Mn(III) N-alkylpyridylporphyrin-based superoxide dismutase (SOD) mimics has a major impact on their in vivo ability to suppress oxidative stress. Meta isomers are less potent SOD mimics than ortho analogues but are 10-fold ... Full text Link to item Cite

Supraspinal inactivation of mitochondrial superoxide dismutase is a source of peroxynitrite in the development of morphine antinociceptive tolerance.

Journal Article Neuroscience · December 1, 2009 Effective treatment of chronic pain with morphine is limited by decreases in the drug's analgesic action with chronic administration (antinociceptive tolerance). Because opioids are mainstays of pain management, restoring their efficacy has great clinical ... Full text Link to item Cite

The SLCO1B1*5 genetic variant is associated with statin-induced side effects.

Journal Article J Am Coll Cardiol · October 20, 2009 OBJECTIVES: We sought to identify single nucleotide polymorphisms associated with mild statin-induced side effects. BACKGROUND: Statin-induced side effects can interfere with therapy. Single nucleotide polymorphisms in cytochrome P450 enzymes impair statin ... Full text Link to item Cite

Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via suppression of oxidative stress in a mouse model of breast tumor.

Journal Article Free Radic Biol Med · October 1, 2009 MnTE-2-PyP(5+) is a potent catalytic scavenger of reactive oxygen and nitrogen species, primarily superoxide and peroxynitrite. It therefore not only attenuates primary oxidative damage, but was found to modulate redox-based signaling pathways (HIF-1alpha, ... Full text Link to item Cite

Lipophilicity of potent porphyrin-based antioxidants: comparison of ortho and meta isomers of Mn(III) N-alkylpyridylporphyrins.

Journal Article Free Radic Biol Med · July 1, 2009 Mn(III) N-alkylpyridylporphyrins are among the most potent known SOD mimics and catalytic peroxynitrite scavengers and modulators of redox-based cellular transcriptional activity. In addition to their intrinsic antioxidant capacity, bioavailability plays a ... Full text Link to item Cite

Optimizing melphalan pharmacokinetics in regional melanoma therapy: does correcting for ideal body weight alter regional response or toxicity?

Journal Article Ann Surg Oncol · April 2009 BACKGROUND: This study aims to determine what effect correcting melphalan dosing for ideal body weight (IBW) has on toxicity and response in isolated limb infusion (ILI) in patients with advanced extremity melanoma. METHODS: This was an open observational ... Full text Link to item Cite

Effect of lipophilicity of Mn (III) ortho N-alkylpyridyl- and diortho N, N'-diethylimidazolylporphyrins in two in-vitro models of oxygen and glucose deprivation-induced neuronal death.

Journal Article Free Radic Res · April 2009 In vivo investigations have confirmed the beneficial effects of hydrophilic, cationic Mn(III) porphyrin-based catalytic antioxidants in different models of oxidative stress. Using a cell culture model of rat mixed neuronal/glial cells, this study investiga ... Full text Link to item Cite

Lipophilicity is a critical parameter that dominates the efficacy of metalloporphyrins in blocking the development of morphine antinociceptive tolerance through peroxynitrite-mediated pathways.

Journal Article Free Radic Biol Med · January 15, 2009 Severe pain syndromes reduce the quality of life of patients with inflammatory and neoplastic diseases, partly because reduced analgesic effectiveness with chronic opiate therapy (i.e., tolerance) leads to escalating doses and distressing side effects. Per ... Full text Link to item Cite

Pure MnTBAP selectively scavenges peroxynitrite over superoxide: comparison of pure and commercial MnTBAP samples to MnTE-2-PyP in two models of oxidative stress injury, an SOD-specific Escherichia coli model and carrageenan-induced pleurisy.

Journal Article Free Radic Biol Med · January 15, 2009 MnTBAP is often referred to as an SOD mimic in numerous models of oxidative stress. We have recently reported that pure MnTBAP does not dismute superoxide, but commercial or poorly purified samples are able to perform O2.- dismutation with low-to-moderate ... Full text Link to item Cite

How to Measure Oxidative Status in Humans? Part II

Conference FREE RADICAL BIOLOGY AND MEDICINE · January 1, 2009 Link to item Cite

Quality of potent Mn porphyrin-based SOD mimics and peroxynitrite scavengers for pre-clinical mechanistic/therapeutic purposes.

Journal Article J Pharm Biomed Anal · November 4, 2008 Cationic Mn porphyrins are among the most potent SOD mimics and peroxynitrite scavengers. They have been widely and successfully used in different models of oxidative stress and are either progressing towards or are in phase I of clinical trials. The most ... Full text Link to item Cite

Pharmacokinetics of the potent redox-modulating manganese porphyrin, MnTE-2-PyP(5+), in plasma and major organs of B6C3F1 mice.

Journal Article Free Radic Biol Med · October 1, 2008 Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), a potent catalytic superoxide and peroxynitrite scavenger, has been beneficial in several oxidative stress-related diseases thus far examined. Pharmacokinetic studies are essential for the ... Full text Link to item Cite

SOD-like activity of Mn(II) beta-octabromo-meso-tetrakis(N-methylpyridinium-3-yl)porphyrin equals that of the enzyme itself.

Journal Article Arch Biochem Biophys · September 1, 2008 Mn porphyrins are among the most efficient SOD mimics with potency approaching that of SOD enzymes. The most potent ones, Mn(III) N-alkylpyridylporphyrins bear positive charges in a close proximity to the metal site, affording thermodynamic and kinetic fac ... Full text Link to item Cite

Phase I evaluation of gemcitabine, mitoxantrone, and their effect on plasma disposition of fludarabine in patients with relapsed or refractory acute myeloid leukemia.

Journal Article Leuk Lymphoma · August 2008 Our aim was to estimate the duration of maximum tolerated dose (MTD) duration for gemcitabine given as a continuous infusion in combination with fludarabine and mitoxantrone and to evaluate potential pharmacokinetic (PK) interactions in 17 patients with re ... Full text Link to item Cite

Impact of electrostatics in redox modulation of oxidative stress by Mn porphyrins: protection of SOD-deficient Escherichia coli via alternative mechanism where Mn porphyrin acts as a Mn carrier.

Journal Article Free Radic Biol Med · July 15, 2008 Understanding the factors that determine the ability of Mn porphyrins to scavenge reactive species is essential for tuning their in vivo efficacy. We present herein the revised structure-activity relationships accounting for the critical importance of elec ... Full text Link to item Cite

Redox modulation of oxidative stress by Mn porphyrin-based therapeutics: the effect of charge distribution.

Journal Article Dalton Trans · March 7, 2008 We evaluate herein the impact of positive charge distribution on the in vitro and in vivo properties of Mn porphyrins as redox modulators possessing the same overall 5+ charge and of minimal stericity demand: Mn(III) meso-tetrakis(trimethylanilinium-4-yl)p ... Full text Link to item Cite

Pure manganese(III) 5,10,15,20-tetrakis(4-benzoic acid)porphyrin (MnTBAP) is not a superoxide dismutase mimic in aqueous systems: a case of structure-activity relationship as a watchdog mechanism in experimental therapeutics and biology.

Journal Article J Biol Inorg Chem · February 2008 Superoxide is involved in a plethora of pathological and physiological processes via oxidative stress and/or signal transduction pathways. Superoxide dismutase (SOD) mimics have, thus, been actively sought for clinical and mechanistic purposes. Manganese(I ... Full text Link to item Cite

Fludarabine-based nonmyeloablative stem cell transplantation for sickle cell disease with and without renal failure: clinical outcome and pharmacokinetics.

Journal Article Biol Blood Marrow Transplant · December 2007 End-organ damage is common in patients with sickle cell disease (SCD) thereby limiting the use of allogeneic stem cell transplantation (SCT). We report the outcome of 2 adult SCD patients, 1 with end-stage renal disease (ESRD), who underwent fludarabine-ba ... Full text Link to item Cite

Design and synthesis of manganese porphyrins with tailored lipophilicity: investigation of redox properties and superoxide dismutase activity.

Journal Article Bioorg Med Chem · November 15, 2007 Thirteen new manganese porphyrins and two porphodimethenes bearing one to three different substituents at the meso positions in a variety of architectures have been synthesized. The substituents employed generally are (i) electron-withdrawing to tune the r ... Full text Link to item Cite

Treatment with imatinib improves drug delivery and efficacy in NSCLC xenografts.

Journal Article Br J Cancer · September 17, 2007 Imatinib, an inhibitor of PDGF-Rbeta and other tyrosine kinase receptors, has been shown to decrease microvessel density and interstitial fluid pressure in solid tumours, thereby improving subsequent delivery of small molecules. The purpose of this study w ... Full text Link to item Cite

Pharmacodynamic and pharmacokinetic study of chronic low-dose metronomic cyclophosphamide therapy in mice.

Journal Article Mol Cancer Ther · August 2007 Prolonged, frequently administered low-dose metronomic chemotherapy (LDM) is being explored (pre)clinically as a promising antiangiogenic antitumor strategy. Although appealing because of a favorable side effect profile and mostly oral dosing, LDM involves ... Full text Link to item Cite

Suppression of RelB-mediated manganese superoxide dismutase expression reveals a primary mechanism for radiosensitization effect of 1alpha,25-dihydroxyvitamin D(3) in prostate cancer cells.

Journal Article Mol Cancer Ther · July 2007 Nuclear factor-kappaB provides an adaptive response to protect cancer cells against cytotoxicity induced by redox active therapeutics. RelB is uniquely expressed at a high level in prostate cancer with high Gleason scores. Recently, we showed that the leve ... Full text Link to item Cite

Mn porphyrin-based superoxide dismutase (SOD) mimic, MnIIITE-2-PyP5+, targets mouse heart mitochondria.

Journal Article Free Radic Biol Med · April 15, 2007 The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnIIITE-2-PyP5+ (AEOL-10113) has proven effective in treating oxidative stress-induced conditions including cancer, radiation damage, diabetes, and central nervous system trauma. The ortho cationi ... Full text Link to item Cite

A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral doxil extravasation.

Journal Article Clin Cancer Res · November 15, 2006 PURPOSE: A noninvasive method to monitor intratumoral Doxil delivery in individual patients during targeted tumor therapy is important to predict treatment response. The purpose of this study was to determine if a small tracer dose of technetium-99m (99mTc ... Full text Link to item Cite

New approach to the activation of anti-cancer pro-drugs by metalloporphyrin-based cytochrome P450 mimics in all-aqueous biologically relevant system.

Journal Article J Inorg Biochem · November 2006 The low-molecular weight water-soluble Fe(III) and Mn(III) porphyrins--in biologically relevant phosphate-buffered saline medium with ascorbic acid as a source of electrons, under aerobic conditions but without co-oxidant - catalyze the hydroxylation of an ... Full text Link to item Cite

Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors.

Journal Article Clin Cancer Res · July 1, 2006 PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumor ... Full text Link to item Cite

New PEG-ylated Mn(III) porphyrins approaching catalytic activity of SOD enzyme.

Journal Article Dalton Trans · January 28, 2006 Two new tri(ethyleneglycol)-derivatized Mn(III) porphyrins were synthesized with the aim of increasing their bioavailability, and blood-circulating half-life. These are Mn(III) tetrakis(N-(1-(2-(2-(2-methoxyethoxy)ethoxy)ethyl)pyridinium-2-yl)porphyrin, Mn ... Full text Link to item Cite

A manganese porphyrin superoxide dismutase mimetic enhances tumor radioresponsiveness.

Journal Article Int J Radiat Oncol Biol Phys · October 1, 2005 PURPOSE: To determine the effect of the superoxide dismutase mimetic Mn(III) tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) on tumor radioresponsiveness. METHODS AND MATERIALS: Various rodent tumor (4T1, R3230, B16) and endothelial (SVEC) cell ... Full text Link to item Cite

Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

Journal Article Int J Hyperthermia · June 2005 OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasa ... Full text Link to item Cite

Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(III) porphyrin catalytic antioxidant therapy.

Journal Article Neurosci Lett · August 12, 2004 This study evaluated the effects of the cationic manganese(III) tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin catalytic antioxidant Mn(III)TDE-2-ImP5+ (AEOL 10150) on outcome from spinal cord compression (SCC) in the mouse. C57BL/6J mice were subjected t ... Full text Link to item Cite

Tetrahydrobiopterin rapidly reduces the SOD mimic Mn(III) ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin.

Journal Article Free Radic Biol Med · August 1, 2004 Mn(III) ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin (Mn(III)TE-2-PyP(5+)) effectively scavenges reactive oxygen and nitrogen species in vitro, and protects in vivo, in different rodent models of oxidative stress injuries. Further, Mn(III)TE-2-PyP(5+) w ... Full text Link to item Cite

New class of potent catalysts of O2.-dismutation. Mn(III) ortho-methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins.

Journal Article Dalton Trans · June 7, 2004 Three new Mn(III) porphyrin catalysts of O2.-dismutation (superoxide dismutase mimics), bearing ether oxygen atoms within their side chains, were synthesized and characterized: Mn(III) 5,10,15,20-tetrakis[N-(2-methoxyethyl)pyridinium-2-yl]porphyrin (MnTMOE ... Full text Link to item Cite

A no-laminectomy spinal cord compression injury model in mice.

Journal Article J Neurotrauma · May 2004 The purpose of this study was to develop a minimally invasive recovery model of spinal cord injury in the C57Bl/6J mouse. Without laminectomy, the epidural space was exposed by disruption of the T10-T11 interspinous ligament. Perpendicular to the rostral-c ... Full text Link to item Cite

Flavin-dependent antioxidant properties of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins.

Journal Article Biochem Pharmacol · January 1, 2004 A number of synthetic manganese complexes exhibit both in vitro and in vivo catalytic antioxidant activities. This study reports that the antioxidant potencies of a new series of meso-N,N'-dialkyl-imidazolium substituted manganese(III) porphyrins are depen ... Full text Link to item Cite

Electrostatic contribution in the catalysis of O2*- dismutation by superoxide dismutase mimics. MnIIITE-2-PyP5+ versus MnIIIBr8T-2-PyP+.

Journal Article J Biol Chem · February 28, 2003 The Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (Mn(III)TE-2-PyP(5+)) is a potent superoxide dismutase (SOD) mimic in vitro and was beneficial in rodent models of oxidative stress pathologies. Its high activity has been ascribed to both the favo ... Full text Link to item Cite

Meso tetrakis ortho-, meta-, and para-n-alkylpyridinioporphyrins: Kinetics of copper(II) and zinc(II) incorporation and zinc porphyrin demetalation

Journal Article Journal of Porphyrins and Phthalocyanines · January 1, 2003 The relative reactivities of the tetrakis(N-alkylpyridinium-X-yl)-porphyrins where X = 4 (alkyl = methyl, ethyl, n-propyl), X = 3 (methyl), and X = 2 (methyl, ethyl, n-propyl, n-butyl, n-hexyl, n-octyl) were studied in aqueous solution. From the ionic stre ... Full text Cite

Rotational isomers of N-alkylpyridylporphyrins and their metal complexes. HPLC separation, (1)H NMR and X-ray structural characterization, electrochemistry, and catalysis of O(2)(.-) disproportionation.

Journal Article Inorg Chem · November 4, 2002 Rotational (atropo-) isomers of Mn(III) meso-tetrakis(N-alkylpyridinium-2-yl)porphyrins and corresponding metal-free porphyrin ligands (where alkyl is methyl, ethyl, n-butyl, n-hexyl) and Zn(II) meso-tetrakis(N-methyl(ethyl,n-hexyl)pyridinium-2-yl)porphyri ... Full text Link to item Cite

A small molecular weight catalytic metalloporphyrin antioxidant with superoxide dismutase (SOD) mimetic properties protects lungs from radiation-induced injury.

Journal Article Free Radic Biol Med · September 15, 2002 Radiation therapy (RT) is an important therapeutic modality in the treatment of thoracic tumors. The maximum doses to these tumors are often limited by the radiation tolerance of lung tissues. Lung injury from ionizing radiation is believed to be a consequ ... Full text Link to item Cite

Isomeric N-alkylpyridylporphyrins and their Zn(II) complexes: inactive as SOD mimics but powerful photosensitizers.

Journal Article Arch Biochem Biophys · June 15, 2002 The ortho, meta, and para isomers of cationic N-alkylpyridylporphyrins and their Zn(II) complexes were compared in terms of their photodynamic properties. The ortho Zn(II) complex was found to be the most efficient in causing photooxidation of NADH in vitr ... Full text Link to item Cite

Thermodynamics, kinetics, and mechanism of the stepwise dissociation and formation of Tris(L-lysinehydroxamato)iron(III) in aqueous acid.

Journal Article Inorg Chem · March 25, 2002 pK(a) values for the hydroxamic acid, alpha-NH(3)(+), and epsilon-NH(3)(+) groups of L-lysinehydroxamic acid (LyHA, H(3)L(2+)) were found to be 6.87, 8.89, and 10.76, respectively, in aqueous solution (I = 0.1 M, NaClO(4)) at 25 degrees C. O,O coordination ... Full text Link to item Cite

Manganese(III) meso-tetrakis(ortho-N-alkylpyridyl)porphyrins. Synthesis, characterization, and catalysis of O2/·- dismutation

Journal Article Journal of the Chemical Society, Dalton Transactions · January 1, 2002 A series of ortho isomers of meso-tetrakis(N-alkylpyridyl)porphyrins (alkyl being methyl, ethyl, n-propyl, n-butyl, n-hexyl, and n-octyl) and their Mn(III) complexes were synthesized and characterized by elemental analysis, uv/vis spectroscopy, electrospra ... Full text Cite

Synthesis, ligand pK(a), and Fe(III) complexation constants for a series of bipodal dihydroxamic acids.

Journal Article Inorg Chem · November 5, 2001 The synthesis of four bipodal dihydroxamic acids containing an apical C atom and amide linkages is described, where Ia,b represent "normal" and "retro" hydroxamate isomers: (R)CH[C(=O)NH(CH(2))(2)NHC(=O)(CH(2))(n)()R'](2) (Ia, R = CH(3), R' = N(OH)(C=O)CH( ... Full text Link to item Cite

Manganese(III) biliverdin IX dimethyl ester: a powerful catalytic scavenger of superoxide employing the Mn(III)/Mn(IV) redox couple.

Journal Article Inorg Chem · February 12, 2001 A manganese(III) complex of biliverdin IX dimethyl ester, (MnIIIBVDME)2, was prepared and characterized by elemental analysis, UV/vis spectroscopy, cyclic voltammetry, chronocoulometry, electrospray mass spectrometry, freezing-point depression, magnetic su ... Full text Link to item Cite

Aqueous solution speciation of Fe(III) complexes with dihydroxamate siderophores alcaligin and rhodotorulic acid and synthetic analogues using electrospray ionization mass spectrometry.

Journal Article Inorg Chem · January 1, 2001 Aqueous solutions of Fe3+ complexes of cyclic (alcaligin) and linear (rhodotorulic acid) dihydroxamate siderophores and synthetic linear eight-carbon-chain and two-carbon-chain dihydroxamic acids ([CH3N(OH)C=O)]2(CH2)n; H2Ln; n = 2 and 8) were investigated ... Full text Link to item Cite

Nitrosylation of manganese(II) tetrakis(N-ethylpyridinium-2-yl)porphyrin: a simple and sensitive spectrophotometric assay for nitric oxide.

Journal Article Nitric Oxide · October 2000 Reaction between NO(*) and manganese tetrakis(N-ethylpyridinium-2-yl)porphyrin (Mn(III)TE-2-PyP(5+)) was investigated at 25 degrees C. At high excess of NO(*) (1.5 mM) the reaction with the oxidized, air-stable form Mn(III)TE-2-PyP(5+) (5 microM), proceeds ... Full text Link to item Cite

Lucigenin: redox potential in aqueous media and redox cycling with O-(2) production.

Journal Article Arch Biochem Biophys · January 15, 2000 The use of lucigenin luminescence as a measure of ¿O-(2) has been questioned because lucigenin has been shown to be capable of mediating the production of O-(2). This being the case, lucigenin can signal the presence of O-(2) even in systems not producing ... Full text Link to item Cite

Catalytic scavenging of peroxynitrite by isomeric Mn(III) N-methylpyridylporphyrins in the presence of reductants.

Journal Article Chem Res Toxicol · May 1999 Three isomers of manganese(III) 5,10,15, 20-tetrakis(N-methylpyridyl)porphyrin (MnTMPyP) were evaluated for their reaction with peroxynitrite. The Mn(III) complexes reacted with peroxynitrite anion with rate constants of 1.85 x 10(7), 3.82 x 10(6), and 4.3 ... Full text Link to item Cite

Electrochemical Behavior of the Fe(III) Complexes of the Cyclic Hydroxamate Siderophores Alcaligin and Desferrioxamine E.

Journal Article Inorg Chem · February 8, 1999 The redox behavior of Fe(III) complexes of the cyclic hydroxamate siderophores alcaligin and desferrioxamine E was investigated by cyclic voltammetry. The limiting, pH independent redox potential (E(1/2) vs NHE) is -446 mV for alcaligin above pH 9 and -477 ... Full text Link to item Cite

Relationship among redox potentials, proton dissociation constants of pyrrolic nitrogens, and in vivo and in vitro superoxide dismutating activities of manganese(III) and iron(III) water-soluble porphyrins

Journal Article Inorganic Chemistry · January 1, 1999 The log kcat values for the dismutation of O2- by a series of monohydroxoiron(III) and aquamanganese(III) porphyrins, including ortho, meta, and para isomers of 5,10,15,20-tetrakis(N-alkylpyridiniumyl)porphyrins, were found to vary linearly with the metal- ... Full text Cite

Bulk liquid membrane transport of ferrioxamine B by neutral and ionizable carriers

Journal Article Journal of the Chemical Society - Dalton Transactions · December 7, 1998 Bulk liquid membrane (BLM) transport of ferrioxamine B (FeHDFB+) across an artificial hydrophobia membrane facilitated by neutral and ionizable carriers was studied. Under controlled conditions, ferrioxamine B transport by neutral ionophores follows a simp ... Full text Cite

The ortho effect makes manganese(III) meso-tetrakis(N-methylpyridinium-2-yl)porphyrin a powerful and potentially useful superoxide dismutase mimic.

Journal Article J Biol Chem · September 18, 1998 The ortho, meta, and para isomers of manganese(III) 5,10,15, 20-tetrakis(N-methylpyridyl)porphyrin, MnTM-2-PyP5+, MnTM-3-PyP5+, and MnTM-4-PyP5+, respectively, were analyzed in terms of their superoxide dismutase (SOD) activity in vitro and in vivo. The im ... Full text Link to item Cite

Lariat Ether Carboxylic Acids as Ionizable Hosts in the Second Coordination Sphere of the Siderophore Ferrioxamine B in Chloroform

Journal Article Inorganic Chemistry · January 1, 1998 A new series of lariat ether carboxylic acids (LnCOOH) was synthesized with different lengths of side arm (6, 9, and 12 atom spacers between the benzo-18-crown-6 crown ether ring and the carboxylic acid functional group). These lariat ethers were used as n ... Full text Cite

A potent superoxide dismutase mimic: manganese beta-octabromo-meso-tetrakis-(N-methylpyridinium-4-yl) porphyrin.

Journal Article Arch Biochem Biophys · July 15, 1997 Variously modified metalloporphyrins offer a promising route to stable and active mimics of superoxide dismutase (SOD). Here we explore bromination on the pyrroles as a means of increasing the redox potentials and the catalytic activities of the copper and ... Full text Link to item Cite

Solvent effect on second-sphere coordination of ferrioxamine B with substituted 18-crown-6 and 30-crown-10 crown ethers in dichloromethane as compared to chloroform

Journal Article Inorganica Chimica Acta · July 15, 1997 Stability constants for the second-sphere association of picrate and perchlorate salts of ferrioxamine B (FeHDFB+) with the substituted crown ethers (CE) 18-crown-6, cis-dicyclohexano-18-crown-6, benzo-18-crown-6, dibenzo-18-crown-6 and dibenzo-30-crown-10 ... Full text Cite

Molecular recognition of stable metal complexes through second-sphere coordination by macrocycles

Journal Article Pure and Applied Chemistry · January 1, 1996 An investigation of second coordination shell complexation of ferrioxamine B by crown ethers, natural ionophores, and other macrocycles through host-guest complexation of the pendant protonated amine group is presented. The influence of guest structure, ho ... Full text Cite

Stereochemical factors affecting second-sphere co-ordination of ferrioxamine B with cis-syn-cis and cis-anti-cis isomers of dicyclohexano-18-crown-6 in chloroform and a comparison with alkali-metal and ammonium cations

Journal Article Journal of the Chemical Society, Dalton Transactions · December 1, 1995 Second-sphere co-ordination of ferrioxamine B [Fe(HL)]+ by dicyclohexano-18-crown-6 (eicosahydrodibenzo[b,k][1,4,7,10,13,16]hexaoxacyclooctadecine) occurs through host-guest complex formation with the protonated amine side chain (CH2)5NH3+. The influence o ... Full text Cite

Hydrolysis of Ferrioxamine B in Aqueous Micellar Solution

Journal Article Inorganic Chemistry · July 1, 1994 The association constant for the Fe(III) complex of the linear trihydroxamic acid siderophore ferrioxamine B (FeHDFB+; HDFB2- = H3N-[(CH2)5-N(O)C(O)-(CH2)2C(O)NH-)]2(CH2)5-N(O)C(O)-CH3) binding to sodium dodecyl sulfate (SDS) micelles was determined by ult ... Full text Cite

Supramolecular Assembly Formation of Ferrioxamine B and Its Al(III), Ga(III), and In(III) Analogues with Dicyclohexano-18-Crown-6 in Chloroform

Journal Article Journal of the American Chemical Society · June 1, 1994 We have shown that the crown ether dicyclohexano-18-crown-6 recognizes the terminal amine group of deferriferrioxamine B (H4DFB+) and its Al(III), Ga(III), Fe(III), and In(III) complexes (MHDFB+) by host-guest complex formation. Host-guest formation consta ... Full text Cite

Functional and chemical characterization of the aging process of an igniter

Journal Article Propellants, Explosives, Pyrotechnics · January 1, 1993 The igniter consisting of 34% Mg, 60% KNO3, 3% KClO4 and 3% organic binder was subjected to accelerated aging under the conditions of 85% relative humidity at 65°C, 75°C and 85°C, and at 75°C with 92% relative humidity. Chemical aging was followed through ... Full text Cite

The stability characterization of the pyrotechnic system. The degradation of the nitrate oxidant in the presence of the magnesium under the accelerated aging conditions

Journal Article Propellants, Explosives, Pyrotechnics · January 1, 1992 The degradation of the nitrate oxidant was followed in the course of the aging process of tracer pyrotechnic mix containing 22.0 % Mg, 46.0 % Sr(NO3)2, 22.0 % KCIO4, 9.0 % Al‐Mg alloy and 4.0 % organic binder. The accelerated aging was conducted under the ... Full text Cite