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

Autor: Cook BN; Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877, USA. brian.cook@boehringer-ingelheim.com, Bentzien J, White A, Nemoto PA, Wang J, Man CC, Soleymanzadeh F, Khine HH, Kashem MA, Kugler SZ Jr, Wolak JP, Roth GP, De Lombaert S, Pullen SS, Takahashi H
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2009 Feb 01; Vol. 19 (3), pp. 773-7. Date of Electronic Publication: 2008 Dec 10.
DOI: 10.1016/j.bmcl.2008.12.028
Abstrakt: 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: MEDLINE
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