NHI-2 (1269802-97-2) is a selective inhibitor of Lactate Dehydrogenase A (LDHA) – IC50 in vitro = 14.7 μM (NADH), 10.5 μM (Pyruvate).1 NHI-2 has also shown cellular growth inhibitory effects against pancreatic cancer cells (PANC-1 cells IC50 = 22.2 μM normoxic and 4.0 μM hypoxic; LPC006 cells IC50 = 17.8 μM normoxic and 1.1 μM hypoxic) with increased efficacy in a cancer cells hypoxic environment.2 LDHA is a key enzyme involved in the Warburg effect and a cancer cells ability to survive in a hypoxic environment.
1) Granchi et al., (2013), Assessing the differential action on cancer cells of LDH-A inhibitors based on the N-hydroxyindole-2-carboxylate (NHI) and malonic (MaI) scaffolds; Org. Biomol. Chem., 11 6588
2) Maftouh et al. (2014), Synergistic interaction of novel lactate dehydrogenase inhibitors with gemcitabine against pancreatic cancer cells in hypoxia; Br. J. Cancer, 110 172
3) Granchi et al. (2011), Discovery of N-Hydroxyindole-based Inhibitors of Human Lactate Dehydrogenase Isoform A (LDH-A) as Starvation Agents against Cancer Cells; J. Med. Chem., 54 1599
4) Allison et al. (2014), Identification of LDH-A as a therapeutic target for cancer cell killing via (i) p53/NAD(H)-dependent and (ii) p-53-independent pathways; Oncogenesis, 3 e102
5) Lea et al. (2016) Inhibition of growth by combined treatment with inhibitors of Lactate Dehydrogenase and either Phenformin of Inhibitors of 6-Phosphofructo-2-kinase / Fructose-2,6-bisphosphatase 3; Anticancer Research, 36 1479 [Focus Biomolecules Citation]