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. 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 (Cay-10483) in EGFR-driven non-small cell lung cancer (NSCLC) in vitro and in xenografts.Formal Name: N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-2-pyridineacetamide. CAS Number: 1439399-58-2. Synonyms: GLS1 Inhibitor III, Telaglenastat. Molecular Formula: C26H24F3N7O3S. Formula Weight: 571.6. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 10 mg/ml, DMSO: 20 mg/ml, DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml. lambdamax: 243 nm. SMILES: O=C(CC1=CC=CC(OC(F)(F)F)=C1)NC2=CC=C(CCCCC3=NN=C(NC(CC4=NC=CC=C4)=O)S3)N=N2. InChi Code: InChI=1S/C26H24F3N7O3S/c27-26(28,29)39-20-9-5-6-17(14-20)15-22(37)31-21-12-11-18(33-34-21)7-1-2-10-24-35-36-25(40-24)32-23(38)16-19-8-3-4-13-30-19/h3-6,8-9,11-14H,1-2,7,10,15-16H2,(H,31,34,37)(H,32,36,38). InChi Key: PRAAPINBUWJLGA-UHFFFAOYSA-N.