title: 3D-QSAR studies of pyruvate dehydrogenase kinase inhibitors based on a divide and conquer strategy.
abstract: PDHK is a highly specific enzyme, which inhibits PDC thereby reducing the conversion of pyruvate to AcetylCoA leading to increased glucose and lactate level contributing to various pathological disease states. 3D-QSAR CoMFA studies were performed on diverse PDHK inhibitors based on maximum common substructural alignments of different classes of molecules with the selected reference molecule using a divide and conquer strategy. Statistically robust CoMFA model was obtained with a cross-validated correlation coefficient of 0.561 and conventional correlation coefficient of 0.990. Predictive correlation coefficient r2(pred) was found to be 0.875.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar (Mohali) 160062, India.
authors.forename: Teshome Leta
authors.initials: TL
authors.lastname: Aboye
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Sobhia
authors.forename: Prasad V
authors.initials: PV
authors.lastname: Bharatam
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D021281:Quantitative Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases