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

Andrew D. Cansfield, Tammy Ladduwahetty, Mihiro Sunose, Katie Ellard, Rosemary Lynch, Anthea L. Newton, Ann Lewis, Gavin Bennett, Nico Zinn, Douglas W. Thomson, Anne J. Rüger, John T. Feutrill, Oliver Rausch, Alan P. Watt, Giovanna Bergamini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)768-773
Number of pages6
JournalACS Medicinal Chemistry Letters
Volume7
Issue number8
DOIs
Publication statusPublished - 11 Aug 2016

Keywords

  • collagen induced arthritis model
  • inflammation
  • kinase inhibitor
  • mTOR

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