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Beschreibung

A cell-permeable, non-cytotoxic N-hydroxyindole (NHI) carboxylate that acts as a potent, reversible, and isoform selective inhibitor of lactic dehydrogenase (LDH) A/LDH-1. Inhibition appears to be competitive with respect to both pyruvate (Ki = 4.7 µ,M) and NADH (cofactor, Ki = 8.9 µ,M). Acts by occupying the whole substrate pocket and part of the cofactor pocket of LDH-A. Blocks the growth of various cancer cell lines by causing an arrest at G1 phase and inducing apoptosis (IC50 = 10.8, 10.6, 11.4, and 31.5 µ,M for A2780/cOHP, MSTO-211H, NIH-H28, and H630 cells, respectively). Exhibits enhanced anticancer activity under hypoxic conditions (GI50 = 0.90 µ,M/hypoxia vs. 16.3 µ,M/normoxia in LPC006 cultures) and strongly synergizes with gemcitabine (Cat. No. 504594).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., A cell-permeable, noncytotoxic NHI (N-hydroxyindole) carboxylate that acts as an isoform A-selective LDH inhibitor (87% inhibition of hLDH-A4 vs 11% inhibition of hLDH-B4 at 125 µ,M, [NADH] = 25 µ,M & [pyruvate] = 2 mM) in a competitive manner with respect to both NADH (Ki = 8.9 µ,M, [pyruvate] = 2 mM) and pyruvate (Ki = 4.7 µ,M, [NADH] = 200 µ,M). Shown to effectively inhibit de novo D-[1,6-13C2] glucose-derived lactate production in HeLa cultures (80% and <5% of control Lac/Glu ratio in 12 h, respectively, with 400 and 500 µ,M inhibitor) and exhibit enhanced anticancer activity under hypoxic conditions (GI50 by SRB assays = 0.90 µ,M/hypoxia vs. 16.3 µ,M/normoxia in LPC006 cultures), while diplaying little antiproliferation activity toward non-tumorigenic hTERT-HPNE (ductal pancreatic) and Hs27 (skin fibroblast) even at concentrations as high as 100 µ,M,., A cell-permeable, both NADH and pyruvate-competitive isoform A-selective LDH inhibitor. Exhibits enhanced anticancer activity under hypoxic conditions.