AI Article Synopsis
- The study focuses on creating and testing imidazo[4,5-b]pyridines as inhibitors for B-Raf kinase, which is important in cancer signaling pathways.
- These compounds effectively bind to B-Raf in a specific conformation that enhances their selectivity towards the kinase.
- Through structure-activity relationship studies, they optimized these inhibitors, resulting in compound 23, which displayed strong potency and selectivity in both enzyme and cell tests.
Article Abstract
This Letter details the synthesis and evaluation of imidazo[4,5-b]pyridines as inhibitors of B-Raf kinase. These compounds bind in a DFG-in, αC-helix out conformation of B-Raf, which is a binding mode associated with significant kinase selectivity. Structure-activity relationship studies involved optimization of the ATP-cleft binding region of these molecules, and led to compound 23, an inhibitor with excellent enzyme/cell potency, and kinase selectivity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2013.08.086 | DOI Listing |
Publication Analysis
Top Keywords
inhibitors b-raf
8
b-raf kinase
8
kinase selectivity
8
imidazo[45-b]pyridine inhibitors
4
kinase
4
kinase letter
4
letter details
4
details synthesis
4
synthesis evaluation
4
evaluation imidazo[45-b]pyridines
4
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!