title: CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model.
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.
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Andrew D
authors: AD
authors: Cansfield
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Tammy
authors: T
authors: Ladduwahetty
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Mihiro
authors: M
authors: Sunose
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Katie
authors: K
authors: Ellard
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Rosemary
authors: R
authors: Lynch
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Anthea L
authors: AL
authors: Newton
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Ann
authors: A
authors: Lewis
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Gavin
authors: G
authors: Bennett
authors: Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors: Nico
authors: N
authors: Zinn
authors: Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors: Douglas W
authors: DW
authors: Thomson
authors: Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors: Anne J
authors: AJ
authors: Rüger
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: John T
authors: JT
authors: Feutrill
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Oliver
authors: O
authors: Rausch
authors: Cellzome Ltd , Chesterford Research Park, Saffron Waldon, CB10 1XL, United Kingdom.
authors: Alan P
authors: AP
authors: Watt
authors: Cellzome AG , Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors: Giovanna
authors: G
authors: Bergamini
keywords: collagen induced arthritis model; inflammation; kinase inhibitor; mTOR