Discovery of potent inhibitors of interleukin-2 inducible T-cell kinase (ITK) through structure-based drug design

Autor:	John P. Wolak, Ji Wang, Hnin Hnin Khine, Peter Allen Nemoto, Chuk Chui Man, Stéphane De Lombaert, Steven S. Pullen, Hidenori Takahashi, Brian Nicholas Cook, Mohammed A. Kashem, Jörg Bentzien, Andre White, Gregory P. Roth, Fariba Soleymanzadeh, Stanley Kugler
Rok vydání:	2008
Předmět:	Drug Molecular model Pyridines media_common.quotation_subject Chemistry Pharmaceutical Clinical Biochemistry Amino Acid Motifs Anti-Inflammatory Agents Molecular Conformation Pharmaceutical Science Crystallography X-Ray Biochemistry Inhibitory Concentration 50 Structure-Activity Relationship Interleukin-2-Inducible T-Cell Kinase Drug Discovery Humans Enzyme Inhibitors Molecular Biology media_common chemistry.chemical_classification Kinase Chemistry Organic Chemistry Protein-Tyrosine Kinases In vitro Cell biology Enzyme Tec kinase Models Chemical Drug Design Molecular Medicine Structure based Benzimidazoles
Zdroj:	Bioorganicmedicinal chemistry letters. 19(3)
ISSN:	1464-3405
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6fe75d81be2fbcce7cd52565bd9aa148 https://pubmed.ncbi.nlm.nih.gov/19111460 Zobrazit plný text záznamu Full Text from ScienceDirect