- Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.
Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.
Journal of medicinal chemistry (2020-10-30)
Michael J Soth, Kang Le, Maria Emilia Di Francesco, Matthew M Hamilton, Gang Liu, Jason P Burke, Chris L Carroll, Jeffrey J Kovacs, Jennifer P Bardenhagen, Christopher A Bristow, Mario Cardozo, Barbara Czako, Elisa de Stanchina, Ningping Feng, Jill R Garvey, Jason P Gay, Mary K Geck Do, Jennifer Greer, Michelle Han, Angela Harris, Zachary Herrera, Sha Huang, Virginia Giuliani, Yongying Jiang, Sarah B Johnson, Troy A Johnson, Zhijun Kang, Paul G Leonard, Zhen Liu, Timothy McAfoos, Meredith Miller, Pietro Morlacchi, Robert A Mullinax, Wylie S Palmer, Jihai Pang, Norma Rogers, Charles M Rudin, Hannah E Shepard, Nakia D Spencer, Jay Theroff, Qi Wu, Alan Xu, Ju Anne Yau, Giulio Draetta, Carlo Toniatti, Timothy P Heffernan, Philip Jones
PMID33118821
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.
MATERIALS
Product Number
Brand
Product Description
Sigma-Aldrich
L-Glutamate Oxidase from Streptomyces sp., recombinant, expressed in E. coli, lyophilized powder, ≥5.0 units/mg solid
Sigma-Aldrich
Peroxidase from horseradish, Type VI, essentially salt-free, lyophilized powder, ≥250 units/mg solid (using pyrogallol)