Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.
Publication
, Journal Article
Frankowski, KJ; Hedrick, MP; Gosalia, P; Li, K; Shi, S; Whipple, D; Ghosh, P; Prisinzano, TE; Schoenen, FJ; Su, Y; Vasile, S; Sergienko, E ...
Published in: ACS Chem Neurosci
March 21, 2012
Herein we present the outcome of a high throughput screening (HTS) campaign-based strategy for the rapid identification and optimization of selective and general chemotypes for both kappa (κ) opioid receptor (KOR) activation and inhibition. In this program, we have developed potent antagonists (IC(50) < 120 nM) or agonists of high binding affinity (K(i) < 3 nM). In contrast to many important KOR ligands, the compounds presented here are highly modular, readily synthesized and, in most cases, achiral. The four new chemotypes hold promise for further development into chemical tools for studying the KOR or as potential therapeutic lead candidates.
Duke Scholars
Altmetric Attention Stats
Dimensions Citation Stats
Published In
ACS Chem Neurosci
DOI
EISSN
1948-7193
Publication Date
March 21, 2012
Volume
3
Issue
3
Start / End Page
221 / 236
Location
United States
Related Subject Headings
- 3404 Medicinal and biomolecular chemistry
- 3401 Analytical chemistry
- 3101 Biochemistry and cell biology
- 0304 Medicinal and Biomolecular Chemistry
Citation
APA
Chicago
ICMJE
MLA
NLM
Frankowski, K. J., Hedrick, M. P., Gosalia, P., Li, K., Shi, S., Whipple, D., … Aubé, J. (2012). Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy. ACS Chem Neurosci, 3(3), 221–236. https://doi.org/10.1021/cn200128x
Frankowski, Kevin J., Michael P. Hedrick, Palak Gosalia, Kelin Li, Shenghua Shi, David Whipple, Partha Ghosh, et al. “Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.” ACS Chem Neurosci 3, no. 3 (March 21, 2012): 221–36. https://doi.org/10.1021/cn200128x.
Frankowski KJ, Hedrick MP, Gosalia P, Li K, Shi S, Whipple D, et al. Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy. ACS Chem Neurosci. 2012 Mar 21;3(3):221–36.
Frankowski, Kevin J., et al. “Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy.” ACS Chem Neurosci, vol. 3, no. 3, Mar. 2012, pp. 221–36. Pubmed, doi:10.1021/cn200128x.
Frankowski KJ, Hedrick MP, Gosalia P, Li K, Shi S, Whipple D, Ghosh P, Prisinzano TE, Schoenen FJ, Su Y, Vasile S, Sergienko E, Gray W, Hariharan S, Milan L, Heynen-Genel S, Mangravita-Novo A, Vicchiarelli M, Smith LH, Streicher JM, Caron MG, Barak LS, Bohn LM, Chung TDY, Aubé J. Discovery of Small Molecule Kappa Opioid Receptor Agonist and Antagonist Chemotypes through a HTS and Hit Refinement Strategy. ACS Chem Neurosci. 2012 Mar 21;3(3):221–236.
Published In
ACS Chem Neurosci
DOI
EISSN
1948-7193
Publication Date
March 21, 2012
Volume
3
Issue
3
Start / End Page
221 / 236
Location
United States
Related Subject Headings
- 3404 Medicinal and biomolecular chemistry
- 3401 Analytical chemistry
- 3101 Biochemistry and cell biology
- 0304 Medicinal and Biomolecular Chemistry