Structural highlights
Publication Abstract from PubMed
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.
Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery.,Medina JR, Blackledge CW, Heerding DA, Campobasso N, Ward P, Briand J, Wright L, Axten JM ACS Med Chem Lett. 2010 Jul 22;1(8):439-42. doi: 10.1021/ml100136n. eCollection, 2010 Nov 11. PMID:24900229[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Medina JR, Blackledge CW, Heerding DA, Campobasso N, Ward P, Briand J, Wright L, Axten JM. Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery. ACS Med Chem Lett. 2010 Jul 22;1(8):439-42. doi: 10.1021/ml100136n. eCollection, 2010 Nov 11. PMID:24900229 doi:http://dx.doi.org/10.1021/ml100136n
