A cell-permeable, orally available thiadiazolyl-butyl-pyridazinyl compound that acts as a potent, selective, time-dependent, and slowly-reversible (t1/2 = 45 min at 25 C) inhibitor of glutaminase (IC50 = 45, 23 and 28 nM for rec hu-GAC, KGA and GAC, respectively). The inhibition appears to be non-competitive and allosteric. Exhibits anti-proliferative effects in HCC1806 and MDA-MB-231 triple-negative breast cancer cell lines (IC50 = 49 and 26 nM, respectively), but does not affect the viability of ER+/HER2-T47D cell line. Shown to reduce glutamine consumption (IC50 = 17 nM) and glutamate production (IC50 = 15 nM) rates in HCC1806 cells. Inhibits the growth of HCC1806 xenografts in mice (~200 mg/kg, p.o., b.i.d) and of JIMT-1 xenografts (200 mg/kg p.o., b.i.d), either alone or in combination with paclitaxel (10 mg/kg , 5 doses alternate days).Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Synonyms: GLS1 Inhibitor III, CB-839 - CAS 1439399-58-2 - Calbiochem; N-(6-(4-(5-((2-Pyridin-2-ylacetyl)amino)-1,3,4-thiadiazol-2-yl)butyl)pyridazin-3-yl)-2-(3-(trifluoromethoxy)phenyl)acetamide, KGA Inhibitor III, 2-(Pyridin-2-yl)-N-(5-(4-(6-(2-(3-(trifluoromethoxy)phenyl)acetamido)pyridazin-3-yl)butyl)-1,3,4-thiadiazol-2
Molecular Formula: C26H24F3N7O3S
Molecular Weight: 571.57
Linear Structural Formula: C26H24F3N7O3S
Purity: >=97% (HPLC)
Biochem Physiol Actions: Target IC50: 23 nM & 28 nM, respectively, using murine kidney and brain homogenates
Legal Information: CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Other Notes: Gross, M.I., et al. 2014. Mol. Cancer Ther.13, 890.