Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery
- GSKNC
Fragment screening of phosphoinositide-dependent kinase-1 (PDK1) in a biochemical kinase assay afforded hits that were characterized and prioritized based on ligand efficiency and binding interactions with PDK1 as determined by NMR. Subsequent crystallography and follow-up screening led to the discovery of aminoindazole 19, a potent leadlike PDK1 inhibitor with high ligand efficiency. Well-defined structure-activity relationships and protein crystallography provide a basis for further elaboration and optimization of 19 as a PDK1 inhibitor.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
- Sponsoring Organization:
- INDUSTRY
- OSTI ID:
- 1025641
- Journal Information:
- ACS Med. Chem. Lett., Vol. 1, Issue (8) ; 11, 2010
- Country of Publication:
- United States
- Language:
- ENGLISH
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