An orally bioavailable noncompetitive inhibitor of GLS1; inhibits GAC (IC50s 50s = 28 and 23 nM

CB-839 – 25 mg

Brand:
Cayman
CAS:
1439399-58-2
Storage:
-20
UN-No:
Non-Hazardous - /

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.{35064} 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.{35065,35066,35067}  

 

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Description

An orally bioavailable noncompetitive inhibitor of GLS1; inhibits GAC (IC50s 50s = 28 and 23 nM, respectively for brain and kidney) compared to GLS2 (IC50 > 1,000 nM for liver); antiproliferative against TNBC cell lines HCC1806 and MDA-MB-231 (IC50s = 49 and 26 nM, respectively), but not against estrogen receptor-positive cells T47D (IC50 > 1,000 nM); inhibits tumor growth by 61% in a patient-derived TNBC xenograft model (200 mg/kg, p.o.); antiproliferative against AML and in synergy with erlotinib against EGFR-driven NSCLC

Formal name: N-[5-[4-[6-[[2-[3-(trifluoromethoxy)phenyl]acetyl]amino]-3-pyridazinyl]butyl]-1,3,4-thiadiazol-2-yl]-2-pyridineacetamide

Synonyms:  GLS1 Inhibitor III

Molecular weight: 571.6

CAS: 1439399-58-2

Purity: ≥98%

Formulation: A crystalline solid

Product Type|Biochemicals|Small Molecule Inhibitors|Amino Acid Turnover||Research Area|Cancer|Cell Death|Apoptosis||Research Area|Cancer|Cell Signaling|Growth Factor Receptor Signaling||Research Area|Cancer|Metabolism

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