RGNCY-0101 (Compound 4 PDK inhibitor)
Compound 4 is a novel PDKs (pyruvate dehydrogenase kinases) inhibitor. Compound 4 is a pan-isoform PDK inhibitor (EC50 = 0.42 μM) which bound to and inhibited the 4 PDK isoforms. Compound 4 reduced pyruvate dehydrogenase complex phosphorylation in NCI-H1975 in a dose-dependent manner. Moreover, Compound 4 was shown through molecular modelling to dock well in the ATP binding pocket of the 4 PDK isoforms. Cell viability assays showed Compound 4 potently blocked NCI-H1975 cell proliferation (IC50 = 3.32 μM), but did not effect human normal lung cell MRC-5. Compound 4 shows promise in the development of PDKs inhibitors in cancer treatment.
Systematic Name: (S)-2-(5-(1-benzylpiperidin-2-yl)-3-(tetrahydro-2H-pyran-4-yl)-1H-1,2,4-triazol-1-yl)ethan-1-ol
Mol Wt: 370.50
Tags: Cancer, small molecule, Compound 4, RGNCY-0101, PDKs, PDK, pyruvate dehydrogenase kinases, NCI-H1975