LDH-A Inhibitor III, NHI-1

A cell-permeable, both NADH and pyruvate-competitive isoform A-selective LDH inhibitor. Exhibits enhanced anticancer activity under hypoxic conditions.

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 (K_i = 4.7 µM) and NADH (cofactor; K_i = 8.9 µM). 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 µM for A2780/cOHP, MSTO-211H, NIH-H28, and H630 cells, respectively). Exhibits enhanced anticancer activity under hypoxic conditions (GI₅₀ = 0.90 µM/hypoxia vs. 16.3 µM/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 µM; [NADH] = 25 µM & [pyruvate] = 2 mM) in a competitive manner with respect to both NADH (K_i = 8.9 µM; [pyruvate] = 2 mM) and pyruvate (K_i = 4.7 µM; [NADH] = 200 µM). 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 µM inhibitor) and exhibit enhanced anticancer activity under hypoxic conditions (GI₅₀ by SRB assays = 0.90 µM/hypoxia vs. 16.3 µM/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 µM;.

Cell permeable: yes

Primary Target
LDH-A/LDH-1

Target IC₅₀: 10.8, 10.6, 11.4, and 31.5 &micro

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Maftouh, M., et al. 2014. Br. J. Cancer.110, 172.
Granchi, C., et al. 2011. J. Med. Chem.54, 1599.

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