Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties
- J Med Chem. 2020 Nov 12;63(21):12957-12977. doi: 10.1021/acs.jmedchem.0c01398.
- 1. Institute for Applied Cancer Science (IACS), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
- 2. Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION), The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
- 3. Antitumor Assessment Core Facility-Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States.
- 4. Drunkenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York New York 10065, United States.
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.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Glutaminase
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target: Glutaminase
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