title: N-Phenyl-4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R phosphoinositide-3-kinase (PI3Kα).
abstract: This work describes our efforts to optimize the lead PI3Kα inhibitor N-benzyl 4-hydroxy-2-quinolone-3-carboxamide using structure-based design and molecular docking. We identified a series of N-phenyl 4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R versus wild-type PI3Kα and we also showed that the cell growth inhibition by these compounds likely occurs by inhibiting the formation of pAKT and induction of apoptosis.
authors.affiliation: College of Pharmacy, University of Nebraska Medical Center, 986025 Nebraska Medical Center, Omaha, NE 68198-6025, USA.
authors.forename: Dima A
authors.initials: DA
authors.lastname: Sabbah
authors.forename: Neka A
authors.initials: NA
authors.lastname: Simms
authors.forename: Wang
authors.initials: W
authors.lastname: Wang
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Dong
authors.forename: Edward L
authors.initials: EL
authors.lastname: Ezell
authors.forename: Michael G
authors.initials: MG
authors.lastname: Brattain
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Vennerstrom
authors.forename: Haizhen A
authors.initials: HA
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D011804:Quinolines