Document Detail


Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery.
MedLine Citation:
PMID:  24900229     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Jesús R Medina; Charles W Blackledge; Dirk A Heerding; Nino Campobasso; Paris Ward; Jacques Briand; Lois Wright; Jeffrey M Axten
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Publication Detail:
Type:  Journal Article     Date:  2010-07-22
Journal Detail:
Title:  ACS medicinal chemistry letters     Volume:  1     ISSN:  1948-5875     ISO Abbreviation:  ACS Med Chem Lett     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2014-06-05     Completed Date:  2014-06-05     Revised Date:  2014-06-09    
Medline Journal Info:
Nlm Unique ID:  101521073     Medline TA:  ACS Med Chem Lett     Country:  United States    
Other Details:
Languages:  eng     Pagination:  439-42     Citation Subset:  -    
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