Discovery of IPN60090, a clinical stage selective glutaminase-1 (GLS-1) inhibitor with excellent pharmacokinetic and physicochemical properties Journal Article

   

Authors:	Soth, M. J.; Le, K.; Di Francesco, M. E.; Hamilton, M. M.; Liu, G.; Burke, J. P.; Carroll, C. L.; Kovacs, J. J.; Bardenhagen, J. P.; Bristow, C. A.; Cardozo, M.; Czako, B.; De Stanchina, E.; Feng, N.; Garvey, J. R.; Gay, J. P.; Do, M. K. G.; Greer, J.; Han, M.; Harris, A.; Herrera, Z.; Huang, S.; Giuliani, V.; Jiang, Y.; Johnson, S. B.; Johnson, T. A.; Kang, Z.; Leonard, P. G.; Liu, Z.; McAfoos, T.; Miller, M.; Morlacchi, P.; Mullinax, R. A.; Palmer, W. S.; Pang, J.; Rogers, N.; Rudin, C. M.; Shepard, H. E.; Spencer, N. D.; Theroff, J.; Wu, Q.; Xu, A.; Yau, J. A.; Draetta, G.; Toniatti, C.; Heffernan, T. P.; Jones, P.
Article Title:	Discovery of IPN60090, a clinical stage selective glutaminase-1 (GLS-1) inhibitor with excellent pharmacokinetic and physicochemical properties
Abstract:	Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans. © 2020 American Chemical Society. All rights reserved.
Journal Title:	Journal of Medicinal Chemistry
Volume:	63
Issue:	21
ISSN:	0022-2623
Publisher:	American Chemical Society
Date Published:	2020-11-12
Start Page:	12957
End Page:	12977
Language:	English
DOI:	10.1021/acs.jmedchem.0c01398
PUBMED:	33118821
PROVIDER:	scopus
PMCID:	PMC9007139
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85095815489&doi=10.1021%2facs.jmedchem.0c01398&partnerID=40&md5=b7c4ca5712b1b690a321ffe4852381de
Notes:	Article -- Export Date: 4 January 2021 -- Source: Scopus

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