CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model.

Autor: Cansfield AD; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Ladduwahetty T; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Sunose M; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Ellard K; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Lynch R; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Newton AL; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Lewis A; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Bennett G; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Zinn N; Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany., Thomson DW; Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany., Rüger AJ; Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany., Feutrill JT; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Rausch O; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Watt AP; Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom., Bergamini G; Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany.
Jazyk: angličtina
Zdroj: ACS medicinal chemistry letters [ACS Med Chem Lett] 2016 Jun 10; Vol. 7 (8), pp. 768-73. Date of Electronic Publication: 2016 Jun 10 (Print Publication: 2016).
DOI: 10.1021/acsmedchemlett.6b00149
Abstrakt: CZ415, a potent ATP-competitive mTOR inhibitor with unprecedented selectivity over any other kinase is described. In addition to a comprehensive characterization of its activities in vitro, in vitro ADME, and in vivo pharmacokinetic data are reported. The suitability of this inhibitor for studying in vivo mTOR biology is demonstrated in a mechanistic mouse model monitoring mTOR proximal downstream phosphorylation signaling. Furthermore, the compound reported here is the first ATP-competitive mTOR inhibitor described to show efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model.
Databáze: MEDLINE
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