Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties
Michael Soth(The University of Texas MD Anderson Cancer Center), Kang Le(The University of Texas MD Anderson Cancer Center), Maria Emilia Di Francesco(The University of Texas MD Anderson Cancer Center), Matthew M. Hamilton(The University of Texas MD Anderson Cancer Center), Gang Liu(The University of Texas MD Anderson Cancer Center), Jason P. Burke(The University of Texas MD Anderson Cancer Center), Chris L. Carroll(The University of Texas MD Anderson Cancer Center), Jeffrey J. Kovacs(The University of Texas MD Anderson Cancer Center), Jennifer Bardenhagen(The University of Texas MD Anderson Cancer Center), Christopher A. Bristow(The University of Texas MD Anderson Cancer Center), Mario Cardozo(The University of Texas MD Anderson Cancer Center), Barbara Czakó(The University of Texas MD Anderson Cancer Center), Elisa de Stanchina(Memorial Sloan Kettering Cancer Center), Ningping Feng(The University of Texas MD Anderson Cancer Center), Jill R. Garvey(The University of Texas MD Anderson Cancer Center), Jason Gay(The University of Texas MD Anderson Cancer Center), Mary Geck(The University of Texas MD Anderson Cancer Center), Jennifer Greer(The University of Texas MD Anderson Cancer Center), Michelle Han(The University of Texas MD Anderson Cancer Center), Angela L. Harris(The University of Texas MD Anderson Cancer Center), Zachary Herrera(The University of Texas MD Anderson Cancer Center), Sha Huang(The University of Texas MD Anderson Cancer Center), Virginia Giuliani(The University of Texas MD Anderson Cancer Center), Yongying Jiang(The University of Texas MD Anderson Cancer Center), Sarah B. Johnson(The University of Texas MD Anderson Cancer Center), Troy A. Johnson(The University of Texas MD Anderson Cancer Center), Zhijun Kang(The University of Texas MD Anderson Cancer Center), Paul G. Leonard(The University of Texas MD Anderson Cancer Center), Zhen Liu(The University of Texas MD Anderson Cancer Center), Timothy McAfoos(The University of Texas MD Anderson Cancer Center), Meredith A. Miller(The University of Texas MD Anderson Cancer Center), Pietro Morlacchi(The University of Texas MD Anderson Cancer Center), Robert A. Mullinax(The University of Texas MD Anderson Cancer Center), Wylie S. Palmer(The University of Texas MD Anderson Cancer Center), Jihai Pang(The University of Texas MD Anderson Cancer Center), Norma Rogers(The University of Texas MD Anderson Cancer Center), Charles M. Rudin(Memorial Sloan Kettering Cancer Center), Hannah E. Shepard(The University of Texas MD Anderson Cancer Center), Nakia D. Spencer(The University of Texas MD Anderson Cancer Center), Jay Theroff(The University of Texas MD Anderson Cancer Center), Qi Wu(The University of Texas MD Anderson Cancer Center), Alan Xu(The University of Texas MD Anderson Cancer Center), Ju Anne Yau(The University of Texas MD Anderson Cancer Center), Giulio Draetta(The University of Texas MD Anderson Cancer Center), Carlo Toniatti(The University of Texas MD Anderson Cancer Center), Timothy P. Heffernan(The University of Texas MD Anderson Cancer Center), Philip Jones(The University of Texas MD Anderson Cancer Center)
Cited by 90Open Access
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.
Related Papers
No related papers found
Powered by citation graph analysis