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Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
- Source :
-
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 May 15; Vol. 21 (10), pp. 3078-83. Date of Electronic Publication: 2011 Mar 17. - Publication Year :
- 2011
-
Abstract
- We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)
- Subjects :
- Crystallography, X-Ray
Drug Discovery
Enzyme Inhibitors chemistry
Inhibitory Concentration 50
Models, Biological
Molecular Structure
Pyridones chemistry
Pyridones pharmacology
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Small Molecule Libraries pharmacology
Structure-Activity Relationship
Drug Design
Enzyme Activation drug effects
Enzyme Inhibitors pharmacology
Protein Serine-Threonine Kinases antagonists & inhibitors
Small Molecule Libraries chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3405
- Volume :
- 21
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry letters
- Publication Type :
- Academic Journal
- Accession number :
- 21459573
- Full Text :
- https://doi.org/10.1016/j.bmcl.2011.03.032