AI Article Synopsis
- A new group of 3,5-disubstituted indole derivatives has been developed as strong and selective inhibitors targeting all three Pim kinases.
- A high throughput screening technique led to the discovery of a pan-Pim kinase inhibitor with a broad structure.
- Using structure-based drug design, the research identified a unique indole chemical structure that resulted in very potent compounds against Pim-1, Pim-2, and Pim-3, with very low IC(50) values for Pim-1 and Pim-3.
Article Abstract
A series of novel 3,5-disubstituted indole derivatives as potent and selective inhibitors of all three members of the Pim kinase family is described. High throughput screen identified a pan-Pim kinase inhibitor with a promiscuous scaffold. Guided by structure-based drug design, SAR of the series afforded a highly selective indole chemotype that was further developed into a potent set of compounds against Pim-1, 2, and 3 (Pim-1 and Pim-3: IC(50)≤2nM and Pim-2: IC(50)≤100nM).
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| http://dx.doi.org/10.1016/j.bmcl.2011.08.105 | DOI Listing |
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