title: New inhibitor of 3-phosphoinositide dependent protein kinase-1 identified from virtual screening.
abstract: 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been recognized as a promising anticancer target. Thus, it is interesting to identify new inhibitors of PDK1 for anticancer drug discovery. Through a combined use of virtual screening and wet experimental activity assays, we have identified a new PDK1 inhibitor with IC(50)=~200 nM. The anticancer activities of this compound have been confirmed by the anticancer activity assays using 60 cancer cell lines. The obtained new PDK1 inhibitor and its PDK1-inhibitor binding mode should be valuable in future de novo design of novel, more potent and selective PDK1 inhibitors for future development of anticancer therapeutics.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, PR China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Yang
authors.forename: Mohamed Diwan M
authors.initials: MD
authors.lastname: AbdulHameed
authors.forename: Adel
authors.initials: A
authors.lastname: Hamza
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Zhan
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D017346:Protein Serine-Threonine Kinases