Abstract
A novel series of p38 MAP kinase inhibitors with high selectivity for the p38α isoform over the other family members including the highly homologous p38β isoform has been identified. X-ray co-crystallographic studies have revealed an unprecedented kinase binding mode in p38α for representative analogs, 5c and 9d, in which a Leu108/Met109 peptide flip occurs within the p38α hinge region. Based on these findings, a general strategy for the rational design of additional promising p38α isoform selective inhibitors by targeting this novel binding mode is proposed.
Original language | English (US) |
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Pages (from-to) | 4120-4126 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 23 |
Issue number | 14 |
DOIs | |
State | Published - Jul 15 2013 |
All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry