High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

Scott E. Wolkenberg; Zhijian Zhao; James J. Mulhearn; Scott T. Harrison; John M. Sanders; Matthew J. Cato; Aneta Jovanovska; Jacqueline Panigel; Sean P. Cook; Darrell A. Henze; Stefanie A. Kane; George D. Hartman; James C. Barrow

doi:10.1016/j.bmcl.2010.12.115

High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

Scott E. Wolkenberg, Zhijian Zhao, James J. Mulhearn, Scott T. Harrison, John M. Sanders, Matthew J. Cato, Aneta Jovanovska, Jacqueline Panigel, Sean P. Cook, Darrell A. Henze, Stefanie A. Kane, George D. Hartman, James C. Barrow

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

The Merck Fragment Library was screened versus acid-sensing ion channel 3 (ASIC3), a novel target for the treatment of pain. Fragment hits were optimized using two strategies, and potency was improved from 0.7 mM to 3 μM with retention of good ligand efficiency and incorporation of reasonable physical properties, off-target profile, and rat pharmacokinetics.

Original language	English (US)
Pages (from-to)	2646-2649
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	9
DOIs	https://doi.org/10.1016/j.bmcl.2010.12.115
State	Published - May 1 2011
Externally published	Yes

Keywords

Acid-sensing ion channel 3
Electrophysiology
Fragment screening

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2010.12.115

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Wolkenberg, S. E., Zhao, Z., Mulhearn, J. J., Harrison, S. T., Sanders, J. M., Cato, M. J., Jovanovska, A., Panigel, J., Cook, S. P., Henze, D. A., Kane, S. A., Hartman, G. D., & Barrow, J. C. (2011). High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors. Bioorganic and Medicinal Chemistry Letters, 21(9), 2646-2649. https://doi.org/10.1016/j.bmcl.2010.12.115

Wolkenberg, SE, Zhao, Z, Mulhearn, JJ, Harrison, ST, Sanders, JM, Cato, MJ, Jovanovska, A, Panigel, J, Cook, SP, Henze, DA, Kane, SA, Hartman, GD & Barrow, JC 2011, 'High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 9, pp. 2646-2649. https://doi.org/10.1016/j.bmcl.2010.12.115

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abstract = "The Merck Fragment Library was screened versus acid-sensing ion channel 3 (ASIC3), a novel target for the treatment of pain. Fragment hits were optimized using two strategies, and potency was improved from 0.7 mM to 3 μM with retention of good ligand efficiency and incorporation of reasonable physical properties, off-target profile, and rat pharmacokinetics.",

keywords = "Acid-sensing ion channel 3, Electrophysiology, Fragment screening",

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AU - Wolkenberg, Scott E.

AU - Zhao, Zhijian

AU - Mulhearn, James J.

AU - Harrison, Scott T.

AU - Sanders, John M.

AU - Cato, Matthew J.

AU - Jovanovska, Aneta

AU - Panigel, Jacqueline

AU - Cook, Sean P.

AU - Henze, Darrell A.

AU - Kane, Stefanie A.

AU - Hartman, George D.

AU - Barrow, James C.

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KW - Electrophysiology

KW - Fragment screening

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High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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