| Literature DB >> 33118821 |
Michael J Soth1, Kang Le1, Maria Emilia Di Francesco1, Matthew M Hamilton1, Gang Liu1, Jason P Burke1, Chris L Carroll1, Jeffrey J Kovacs2, Jennifer P Bardenhagen1, Christopher A Bristow2, Mario Cardozo1, Barbara Czako1, Elisa de Stanchina3, Ningping Feng2, Jill R Garvey2, Jason P Gay2, Mary K Geck Do1, Jennifer Greer2, Michelle Han1, Angela Harris2, Zachary Herrera1, Sha Huang1, Virginia Giuliani2, Yongying Jiang1, Sarah B Johnson2, Troy A Johnson1, Zhijun Kang1, Paul G Leonard1, Zhen Liu1, Timothy McAfoos1, Meredith Miller2, Pietro Morlacchi1, Robert A Mullinax2, Wylie S Palmer1, Jihai Pang1, Norma Rogers1, Charles M Rudin4, Hannah E Shepard1, Nakia D Spencer2, Jay Theroff1, Qi Wu1, Alan Xu1, Ju Anne Yau1, Giulio Draetta1,2, Carlo Toniatti2, Timothy P Heffernan2, Philip Jones1.
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.Entities:
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Year: 2020 PMID： 33118821 PMCID： PMC9007139 DOI： 10.1021/acs.jmedchem.0c01398
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446