N-Phenyl-4-hydroxy-2-quinolone-3-carboxamides as selective inhibitors of mutant H1047R phosphoinositide-3-kinase (PI3Kα)

Dima A. Sabbah, Neka A. Simms, Wang Wang, Yuxiang Dong, Edward L. Ezell, Michael G. Brattain, Jonathan L. Vennerstrom, Haizhen A. Zhong

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7175-7183
Number of pages9
JournalBioorganic and Medicinal Chemistry
Issue number24
StatePublished - Dec 15 2012


  • AKT phosphorylation
  • Apoptosis
  • Colon cancer
  • PI3K
  • Selectivity

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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