Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.
Basic Information
ID: ALA4673258
Journal: J Med Chem
Title: Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.
Authors: Soth MJ,Le K,Di Francesco ME,Hamilton MM,Liu G,Burke JP,Carroll CL,Kovacs JJ,Bardenhagen JP,Bristow CA,Cardozo M,Czako B,de Stanchina E,Feng N,Garvey JR,Gay JP,Do MKG,Greer J,Han M,Harris A,Herrera Z,Huang S,Giuliani V,Jiang Y,Johnson SB,Johnson TA,Kang Z,Leonard PG,Liu Z,McAfoos T,Miller M,Morlacchi P,Mullinax RA,Palmer WS,Pang J,Rogers N,Rudin CM,Shepard HE,Spencer ND,Theroff J,Wu Q,Xu A,Yau JA,Draetta G,Toniatti C,Heffernan TP,Jones P
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.
CiteXplore: 33118821
DOI: 10.1021/acs.jmedchem.0c01398
Patent ID: ┄