Cayman CB-839

CB-839 is an orally bioavailable noncompetitive inhibitor of the glutaminase 1 (GLS1) splice variants, kidney-type (KGA) and glutaminase C (GAC), which convert glutamine into glutamate.¹ CB-839 inhibits human recombinant GAC with IC₅₀ values of less than 50 nM, varying based on the length of preincubation. It inhibits GLS1 activity in tissue homogenates (IC₅₀s = 28 and 23 nM, respectively for brain and kidney), but it does not inhibit GLS2 (IC₅₀ > 1,000 nM for liver). It possesses antiproliferative activity against the triple-negative breast cancer (TNBC) cell lines HCC1806 and MDA-MB-231 (IC₅₀s = 49 and 26 nM, respectively) but not against estrogen receptor-positive T47D cells (IC₅₀ > 1,000 nM). In a patient-derived TNBC mouse xenograft model, CB-839 (200 mg/kg, p.o.) inhibits tumor growth by 61% relative to vehicle control. It also possesses antiproliferative properties in vitro against acute myeloid leukemia (AML) and in synergy with erlotinib (Item No. 10483) in EGFR-driven non-small cell lung cancer (NSCLC) in vitro and in xenografts.^2,3,4

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