Telaglenastat (CB-839)

Description: Telaglenastat (formerly known as CB-839) is a novel, investigational, potent, selective, and orally bioavailable small molecule glutaminase inhibitor with IC50 of 24 nM for recombinant human GAC. CB-839 exhibits time-dependent and slowly reversible kinetics. IC50 values for glutaminase inhibition by CB-839 following preincubation with rHu-GAC for-1 hour are < 50 nmol/L, at least 13-fold lower than with BPTES. CB-839 has antiproliferative activity in a triple-negative breast cancer (TNBC) cell line, HCC-1806, while no antiproliferative activity is observed in an estrogen receptor–positive cell line, T47D. Telaglenastat is currently in Phase 1 study in combination with cabozantinib in patients with advanced renal cell carcinoma. Telaglenastat is novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. RCC tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care RCC therapies including cabozantinib.

References: Mol Cancer Ther. 2014 Apr; 13(4):890-901.

Publications Citing Use of InvivoChem Telaglenastat (CB-839): https://pdfs.semanticscholar.org/1b30/a76c147bce64b701178d36818c9652661184.pdf; https://www.researchsquare.com/article/rs-117384/v1; DOI: 10.21203/rs.3.rs-117384/v1

Telaglenastat; CB839; CB-839; CB 839;

Chemical Name: 2-(pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1, 3, 4-thiadiazol-2-yl)acetamide

SMILES Code: O=C(NC1=CC=C(CCCCC2=NN=C(NC(CC3=NC=CC=C3)=O)S2)N=N1)CC4=CC(OC(F)(F)F)=CC=C4