Scholars@Duke
Robert Anthony Mook Jr.

Robert Anthony Mook Jr.

Assistant Professor in Medicine
Medicine, Gastroenterology
robert.mook@duke.edu
Genetic Science Research Bldg. 1 Duke Box 3256, 595 LaSalle Street, Room 1063, Durham, NC 27710
905 LaSalle Street , Mailbox 3256, Genetic Science Research Bldg 1, RM1063, Durham, NC 27710

Scholarly Works - Journal articles

Inhibitors of the PqsR Quorum-Sensing Receptor Reveal Differential Roles for PqsE and RhlI in Control of Phenazine Production.

Journal article ACS Chem Biol · June 20, 2025 Pseudomonas aeruginosa is a leading cause of hospital-acquired infections and it is resistant to many current antibiotic therapies, making development of new antimicrobial treatments imperative. The cell-to-cell communication process called quorum sensing ... Full text Link to item Cite

Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy.

Journal article Biochem J · February 8, 2019 The Wnt signaling pathway, known for regulating genes critical to normal embryonic development and tissue homeostasis, is dysregulated in many types of cancer. Previously, we identified that the anthelmintic drug niclosamide inhibited Wnt signaling by prom ... Full text Link to item Cite

Identification of novel triazole inhibitors of Wnt/β-catenin signaling based on the Niclosamide chemotype.

Journal article Bioorg Med Chem Lett · January 15, 2019 Dysregulation of the Wnt signaling pathway is an underlying mechanism in multiple diseases, particularly in cancer. Until recently, identifying agents that target this pathway has been difficult and as a result, no approved drugs exist that specifically ta ... 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

Niclosamide: Beyond an antihelminthic drug.

Journal article Cell Signal · January 2018 Niclosamide is an oral antihelminthic drug used to treat parasitic infections in millions of people worldwide. However recent studies have indicated that niclosamide may have broad clinical applications for the treatment of diseases other than those caused ... Full text Link to item 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

Benzimidazole inhibitors from the Niclosamide chemotype inhibit Wnt/β-catenin signaling with selectivity over effects on ATP homeostasis.

Journal article Bioorg Med Chem · March 15, 2017 The Wnt signaling pathway plays a key role in organ and tissue homeostasis, and when dysregulated, can become a major underlying mechanism of disease, particularly cancer. We reported previously that the anthelmintic drug Niclosamide inhibits Wnt/β-catenin ... Full text Link to item Cite

Discovery of Manassantin A Protein Targets Using Large-Scale Protein Folding and Stability Measurements.

Journal article J Proteome Res · August 5, 2016 Manassantin A is a natural product that has been shown to have anticancer activity in cell-based assays, but has a largely unknown mode-of-action. Described here is the use of two different energetics-based approaches to identify protein targets of manassa ... 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

Perhexiline promotes HER3 ablation through receptor internalization and inhibits tumor growth.

Journal article Breast Cancer Res · December 2015 Human epidermal growth factor receptor HER3 has been implicated in promoting the aggressiveness and metastatic potential of breast cancer. Upregulation of HER3 has been found to be a major mechanism underlying drug resistance to EGFR and HER2 tyrosine kina ... Full text Link to item Cite

Synthesis and Biological Evaluation of Manassantin Analogues for Hypoxia-Inducible Factor 1α Inhibition.

Journal article J Med Chem · October 8, 2015 To cope with hypoxia, tumor cells have developed a number of adaptive mechanisms mediated by hypoxia-inducible factor 1 (HIF-1) to promote angiogenesis and cell survival. Due to significant roles of HIF-1 in the initiation, progression, metastasis, and res ... 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

Small molecule modulators of Wnt/β-catenin signaling.

Journal article Bioorg Med Chem Lett · April 1, 2013 The Wnt signal transduction pathway is dysregulated in many highly prevalent diseases, including cancer. Unfortunately, drug discovery efforts have been hampered by the paucity of targets and drug-like lead molecules amenable to drug discovery. Recently, w ... Full text Link to item Cite

Discovery of dabrafenib: A selective inhibitor of Raf Kinases with antitumor activity against B-Raf-driven tumors

Journal article ACS Medicinal Chemistry Letters · March 14, 2013 Hyperactive signaling of the MAP kinase pathway resulting from the constitutively active B-RafV600E mutated enzyme has been observed in a number of human tumors, including melanomas. Herein we report the discovery and biological evaluation of GS ... Full text Cite

Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling.

Journal article Bioorg Med Chem · November 15, 2012 The Hedgehog signaling pathway plays an essential role in embryo development and adult tissue homeostasis, in regulating stem cells and is abnormally activated in many cancers. Given the importance of this signaling pathway, we developed a novel and versat ... Full text Link to item Cite

The insecticide synergist piperonyl butoxide inhibits hedgehog signaling: assessing chemical risks.

Journal article Toxicol Sci · August 2012 The spread of chemicals, including insecticides, into the environment often raises public health concerns, as exemplified by a recent epidemiologic study associating in utero piperonyl butoxide (PBO) exposure with delayed mental development. The insecticid ... Full text Link to item Cite

Development of potent B-RafV600E inhibitors containing an arylsulfonamide headgroup.

Journal article Bioorg Med Chem Lett · August 1, 2011 A potent series of inhibitors against the B-Raf(V600E) kinase have been developed that show excellent activity in cellular assays and good oral bioavailability in rats. The key structural features of the series are an arylsulfonamide headgroup, a thiazole ... Full text Link to item Cite

Glucocorticoid hedgehog agonists in neurogenesis.

Journal article Vitam Horm · 2011 The process of neurogenesis in mammals, which is prolific and widespread at birth, gradually slows with aging and in humans becomes restricted to areas including the cerebellum and hippocampus. It has been reported that exposure to glucocorticoids can impa ... Full text Link to item Cite

Discovery of an inhibitor of insulin-like growth factor 1 receptor activation: implications for cellular potency and selectivity over insulin receptor.

Journal article Biochem Pharmacol · December 15, 2009 Insulin-like growth factor 1 receptor (IGF-1R) is an attractive target for anti-cancer therapy due to its anti-apoptotic effect on tumor cells, but inhibition of insulin receptor (IR) may have undesired metabolic consequences. The primary sequences of the ... Full text Link to item Cite

Design of potent thiophene inhibitors of polo-like kinase 1 with improved solubility and reduced protein binding.

Journal article Bioorg Med Chem Lett · March 15, 2009 A series of thiophene PLK1 inhibitors was optimized for increased solubility and reduced protein binding through the appendage of basic amine functionality. Interesting selectivity between PLK1 and PLK3 was also obtained through these modifications. ... Full text Link to item Cite

Discovery of thiophene inhibitors of polo-like kinase.

Journal article Bioorg Med Chem Lett · February 1, 2009 The discovery and development of a series of thiophenes as potent and selective inhibitors of PLK is described. Identification and characterization of 2, a useful in vitro PLK inhibitor tool compound, is also presented. ... Full text Link to item Cite

Discovery and optimization of imidazo[1,2-a]pyridine inhibitors of insulin-like growth factor-1 receptor (IGF-1R).

Journal article Bioorg Med Chem Lett · February 1, 2009 The optimization of imidazo[1,2-a]pyridine inhibitors as potent and selective inhibitors of IGF-1R is presented. Further optimization of oral exposure in mice is also discussed. Detailed selectivity, in vitro activity, and in vivo PK profiles of an optimiz ... Full text Link to item Cite

Optimization of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidine IGF-1R tyrosine kinase inhibitors towards JNK selectivity.

Journal article Bioorg Med Chem Lett · January 15, 2009 The SAR of C5' functional groups with terminal basic amines at the C6 aniline of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines is reported. Examples demonstrate potent inhibition of IGF-1R with 1000-fold selectivity over JNK1 and 3 in enzymatic assays. ... Full text Link to item Cite

Discovery of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines: potent inhibitors of the IGF-1R receptor tyrosine kinase.

Journal article Bioorg Med Chem Lett · January 15, 2009 The evaluation of a series of 4,6-bis-anilino-1H-pyrrolo[2,3-d]pyrimidines as inhibitors of the IGF-1R (IGF-IR) receptor tyrosine kinase is reported. Examples demonstrate nanomolar potencies in in vitro enzyme and mechanistic cellular assays as well as pro ... Full text Link to item Cite

Imidazo[5,1-f][1,2,4]triazin-2-amines as novel inhibitors of polo-like kinase 1.

Journal article Bioorg Med Chem Lett · December 1, 2008 The synthesis and biological activities of imidazo[5,1-f][1,2,4]triazin-2-amines (imidazotriazines) as novel polo-like kinase 1 inhibitors are reported. ... Full text Link to item Cite

Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor.

Journal article J Med Chem · August 14, 2008 Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has emerged as one of the most promising new approaches for cancer therapy. We describe herein the key steps starting from an initial screening hit leading to the discovery of pa ... Full text Link to item Cite

In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1.

Journal article Mol Cancer Ther · February 2007 Polo-like kinase 1 (PLK1) plays key roles in the regulation of mitotic progression, including mitotic entry, spindle formation, chromosome segregation, and cytokinesis. PLK1 expression and activity are strongly linked to proliferating cells. Many studies h ... Full text Link to item Cite

Optimization and SAR for dual ErbB-1/ErbB-2 tyrosine kinase inhibition in the 6-furanylquinazoline series.

Journal article Bioorg Med Chem Lett · September 1, 2006 Synthetic modifications on a 6-furanylquinazoline scaffold to optimize the dual ErbB-1/ErbB-2 tyrosine kinase inhibition afforded consistent SAR whereby a 4-(3-fluorobenzyloxy)-3-haloanilino provided the best enzyme potency and cellular selectivity. Change ... Full text Link to item Cite

Preclinical pharmacology of GW280430A (AV430A) in the rhesus monkey and in the cat: a comparison with mivacurium.

Journal article Anesthesiology · April 2004 BACKGROUND: No replacement for succinylcholine is yet available. GW280430A (AV430A) is a representative of a new class of nondepolarizing neuromuscular blocking drugs called asymmetric mixed-onium chlorofumarates. It undergoes rapid degradation in plasma b ... Full text Link to item Cite

Cardiopulmonary effects of the novel neuromuscular blocking drug GW280430A (AV430A) in dogs.

Journal article Anesthesiology · April 2004 BACKGROUND: This investigation determined the cardiopulmonary side effects of a novel nondepolarizing neuromuscular blocking drug with an ultrashort duration of action in anesthetized male beagles. METHODS: The ED95 for GW280430A was first determined in fo ... Full text Link to item Cite

Neuromuscular blocking activity and therapeutic potential of mixed-tetrahydroisoquinolinium halofumarates and halosuccinates in rhesus monkeys.

Journal article J Med Chem · June 5, 2003 Structure-activity relationships in rhesus monkeys for a novel mixed-onium class of ultra-short-acting nondepolarizing tetrahydroisoquinolinium neuromuscular blockers (NMBs) are described. Bis-onium chlorofumarate 20a with (1R,2S)-benzyltetrahydroisoquinol ... Full text Link to item Cite

Stereocontrolled synthesis of cis-dibenzoquinolizine chlorofumarates: curare-like agents of ultrashort duration.

Journal article J Org Chem · May 18, 2001 The quaternizations of dibenzoquinolizines 9 and 14 with 3-halo-1-propanols are highly cis-selective (94-100% cis), results consistent with the N-methylation of O-methylcapaurine (7b), but in contrast to the proposed trans-stereochemistry of dibenzo[a,h]qu ... Full text Link to item Cite

Synthesis of ultra-short-acting neuromuscular blocker GW 0430: a remarkably stereo- and regioselective synthesis of mixed tetrahydroisoquinolinium chlorofumarates.

Journal article Org Lett · December 16, 1999 [formula: see text] The stereo- and regioselective synthesis of ultra-short-acting nondepolarizing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's catalyst, the s ... Full text Link to item Cite

Synthesis and biological activity of a novel series of indole-derived PPARgamma agonists.

Journal article Bioorg Med Chem Lett · December 6, 1999 The synthesis and structure-activity relationships of a novel series of indole 5-carboxylic acids that bind and activate peroxisome proliferator-activated receptor gamma (PPARgamma) are reported. These new analogs are selective for PPARgamma vs the other P ... Full text Link to item Cite

A novel N-aryl tyrosine activator of peroxisome proliferator-activated receptor-gamma reverses the diabetic phenotype of the Zucker diabetic fatty rat.

Journal article Diabetes · July 1999 The discovery that peroxisome proliferator-activated receptor (PPAR)-gamma was the molecular target of the thiazolidinedione class of antidiabetic agents suggested a key role for PPAR-gamma in the regulation of carbohydrate and lipid metabolism. Through th ... Full text Link to item Cite

N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.

Journal article J Med Chem · December 3, 1998 We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo ... Full text Link to item Cite

A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA.

Journal article Proc Natl Acad Sci U S A · April 16, 1996 Development of antisense technology has focused in part on creating improved methods for delivering oligodeoxynucleotides (ODNs) to cells. In this report, we describe a cationic lipid that, when formulated with the fusogenic lipid dioleoylphosphatidylietha ... Full text Link to item Cite

Mechanism of time-dependent inhibition of 5 alpha-reductases by delta 1-4-azasteroids: toward perfection of rates of time-dependent inhibition by using ligand-binding energies.

Journal article Biochemistry · October 17, 1995 Finasteride (17 beta-N-tert-butylcarbamoyl-4-aza-5 alpha-androstan-1-en-3- one) is a time-dependent, apparently irreversible inhibitor of 5 alpha-reductases, but does not fully inhibit the activity of 5 alpha-reductase in vivo. This limited efficacy has be ... Full text Link to item Cite

Synthesis of phenanthridin-3-one derivatives: Non-steroidal inhibitors of steroid 5-α-reductase

Journal article Tetrahedron Letters · June 5, 1995 A short and efficient six-step synthesis of novel phenanthridin-3-one derivatives is described. The synthesis of these derivatives is highlighted by the cyclization of a suitably placed ketone side chain with a thioiminium ion. The derivatives prepared wer ... Full text Cite

6-Azasteroids: structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase.

Journal article J Med Chem · July 22, 1994 6-Azaandrost-4-en-3-ones were synthesized and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase (3BHSD) to explore the structure-activity relatio ... Full text Link to item Cite

Purification of trifluoroacetic anhydride [1]

Journal article Chemical and Engineering News · December 1, 1987 Cite

Vinyl Radical Cyclizations Mediated by the Addition of Stannyl Radicals to Triple Bonds

Journal article Journal of the American Chemical Society · April 1, 1987 Full text Cite

Five vs six membered ring formation in the vinyl radical cyclization

Journal article Tetrahedron Letters · January 1, 1986 The ratio of methylenecyclopentane to methylenecyclohexane derivatives observed in the vinyl radical cyclization increases with the concentration of substrate and tin hydride. This is interpreted to mean that these cyclizations are under thermodynamic cont ... Full text Cite

Free-Radical Cyclization of Bromoacetals. Use in the Construction of Bicyclic Acetals and Lactones

Journal article Journal of the American Chemical Society · January 1, 1983 Full text Cite