Document Detail

Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design.
MedLine Citation:
PMID:  19111460     Owner:  NLM     Status:  MEDLINE    
Interleukin-2 inducible T-cell kinase (ITK) is a member of the Tec kinase family and is involved with T-cell activation and proliferation. Due to its critical role in acting as a modulator of T-cells, ITK inhibitors could provide a novel route to anti-inflammatory therapy. This work describes the discovery of ITK inhibitors through structure-based design where high-resolution crystal structural information was used to optimize interactions within the kinase specificity pocket of the enzyme to improve both potency and selectivity.
Brian N Cook; Jörg Bentzien; Andre White; Peter A Nemoto; Ji Wang; Chuk C Man; Fariba Soleymanzadeh; Hnin Hnin Khine; Mohammed A Kashem; Stanley Z Kugler; John P Wolak; Gregory P Roth; Stéphane De Lombaert; Steven S Pullen; Hidenori Takahashi
Publication Detail:
Type:  Journal Article     Date:  2008-12-10
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  19     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-27     Completed Date:  2010-07-06     Revised Date:  2012-06-01    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  773-7     Citation Subset:  IM    
Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877, USA.
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MeSH Terms
Amino Acid Motifs
Anti-Inflammatory Agents / pharmacology
Benzimidazoles / chemical synthesis,  pharmacology
Chemistry, Pharmaceutical / methods*
Crystallography, X-Ray / methods
Drug Design
Enzyme Inhibitors / chemical synthesis,  pharmacology*
Inhibitory Concentration 50
Models, Chemical
Molecular Conformation
Protein-Tyrosine Kinases / antagonists & inhibitors*,  metabolism*
Pyridines / chemistry
Structure-Activity Relationship
Reg. No./Substance:
0/Anti-Inflammatory Agents; 0/Benzimidazoles; 0/Enzyme Inhibitors; 0/Pyridines; 110-86-1/pyridine; 51-17-2/benzimidazole; EC 2.7.1.-/Tec protein-tyrosine kinase; EC Kinases; EC protein-tyrosine kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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