PDK4-IN-1 hydrochloride

PDK4-IN-1 hydrochloride (CAS No. 2310262-11-2) is a highly selective pyruvate dehydrogenase kinase 4 (PDK4) inhibitor. By directly inhibiting PDK4, it relieves PDK4-mediated phosphorylation and inactivation of pyruvate dehydrogenase (PDH), thereby activating PDH and regulating the PDH signaling pathway as well as mitochondrial energy metabolism and the glycolysis–tricarboxylic acid (TCA) cycle metabolic pathway. This compound exhibits nanomolar IC₅₀ against PDK4 and excellent selectivity over the PDK1/2/3 isoforms. In cell culture, it is used at micromolar concentrations for in vitro metabolism and cell function studies; in animal studies, it is used only for therapeutic interventions in disease models. It is applicable to animal models of metabolic disorders, cardiac hypertrophy, and tumors, and can be administered by intraperitoneal injection or oral dosing.

References:

[1] Lee D, Pagire HS, Pagire SH, Bae EJ, Dighe M, Kim M, Lee KM, Jang YK, Jaladi AK, Jung KY, Yoo EK, Gim HE, Lee S, Choi WI, Chi YI, Song JS, Bae MA, Jeon YH, Lee GH, Liu KH, Lee T, Park S, Jeon JH, Lee IK, Ahn JH. Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases. J Med Chem. 2019 Jan 24;62(2):575-588. doi: 10.1021/acs.jmedchem.8b01168. Epub 2019 Jan 9. Erratum in: J Med Chem. 2019 Mar 14;62(5):2849. doi: 10.1021/acs.jmedchem.9b00249. PMID: 30623649.