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.
Original language | English (US) |
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Pages (from-to) | 7175-7183 |
Number of pages | 9 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 20 |
Issue number | 24 |
DOIs | |
State | Published - Dec 15 2012 |
Keywords
- AKT phosphorylation
- Apoptosis
- Colon cancer
- PI3K
- Selectivity
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry