Literature DB >> 27563401

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

Andrew D Cansfield1, Tammy Ladduwahetty1, Mihiro Sunose1, Katie Ellard1, Rosemary Lynch1, Anthea L Newton1, Ann Lewis1, Gavin Bennett1, Nico Zinn2, Douglas W Thomson2, Anne J Rüger2, John T Feutrill1, Oliver Rausch1, Alan P Watt1, Giovanna Bergamini2.   

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.

Entities:  

Keywords:  collagen induced arthritis model; inflammation; kinase inhibitor; mTOR

Year:  2016        PMID： 27563401      PMCID： PMC4983736          DOI： 10.1021/acsmedchemlett.6b00149

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  24 in total

1.  Mammalian target of rapamycin signaling is crucial for joint destruction in experimental arthritis and is activated in osteoclasts from patients with rheumatoid arthritis.

Authors:  Daniel Cejka; Silvia Hayer; Birgit Niederreiter; Wolfgang Sieghart; Thorsten Fuereder; Jochen Zwerina; Georg Schett
Journal:  Arthritis Rheum       Date:  2010-08

Review 2.  mTOR signaling at a glance.

Authors:  Mathieu Laplante; David M Sabatini
Journal:  J Cell Sci       Date:  2009-10-15       Impact factor: 5.285

3.  Lead- and drug-like compounds: the rule-of-five revolution.

Authors:  Christopher A Lipinski
Journal:  Drug Discov Today Technol       Date:  2004-12

Review 4.  Rapamycin passes the torch: a new generation of mTOR inhibitors.

Authors:  Don Benjamin; Marco Colombi; Christoph Moroni; Michael N Hall
Journal:  Nat Rev Drug Discov       Date:  2011-10-31       Impact factor: 84.694

5.  Effects of orally administered rapamycin in animal models of arthritis and other autoimmune diseases.

Authors:  R P Carlson; W L Baeder; R G Caccese; L M Warner; S N Sehgal
Journal:  Ann N Y Acad Sci       Date:  1993-06-23       Impact factor: 5.691

6.  AZD8055 is a potent, selective, and orally bioavailable ATP-competitive mammalian target of rapamycin kinase inhibitor with in vitro and in vivo antitumor activity.

Authors:  Christine M Chresta; Barry R Davies; Ian Hickson; Tom Harding; Sabina Cosulich; Susan E Critchlow; John P Vincent; Rebecca Ellston; Darren Jones; Patrizia Sini; Dominic James; Zoe Howard; Phillippa Dudley; Gareth Hughes; Lisa Smith; Sharon Maguire; Marc Hummersone; Karine Malagu; Keith Menear; Richard Jenkins; Matt Jacobsen; Graeme C M Smith; Sylvie Guichard; Martin Pass
Journal:  Cancer Res       Date:  2009-12-22       Impact factor: 12.701

7.  Effect of rapamycin on the cyclosporin A-resistant CD28-mediated costimulatory pathway.

Authors:  Paritosh Ghosh; Meredith A Buchholz; Shingo Yano; Dennis Taub; Dan L Longo
Journal:  Blood       Date:  2002-06-15       Impact factor: 22.113

8.  Kinome-wide selectivity profiling of ATP-competitive mammalian target of rapamycin (mTOR) inhibitors and characterization of their binding kinetics.

Authors:  Qingsong Liu; Sivapriya Kirubakaran; Wooyoung Hur; Mario Niepel; Kenneth Westover; Carson C Thoreen; Jinhua Wang; Jing Ni; Matthew P Patricelli; Kurt Vogel; Steve Riddle; David L Waller; Ryan Traynor; Takaomi Sanda; Zheng Zhao; Seong A Kang; Jean Zhao; A Thomas Look; Peter K Sorger; David M Sabatini; Nathanael S Gray
Journal:  J Biol Chem       Date:  2012-01-05       Impact factor: 5.157

Review 9.  mTOR is a key modulator of ageing and age-related disease.

Authors:  Simon C Johnson; Peter S Rabinovitch; Matt Kaeberlein
Journal:  Nature       Date:  2013-01-17       Impact factor: 49.962

10.  The promise and peril of chemical probes.

Authors:  Cheryl H Arrowsmith; James E Audia; Christopher Austin; Jonathan Baell; Jonathan Bennett; Julian Blagg; Chas Bountra; Paul E Brennan; Peter J Brown; Mark E Bunnage; Carolyn Buser-Doepner; Robert M Campbell; Adrian J Carter; Philip Cohen; Robert A Copeland; Ben Cravatt; Jayme L Dahlin; Dashyant Dhanak; Aled M Edwards; Mathias Frederiksen; Stephen V Frye; Nathanael Gray; Charles E Grimshaw; David Hepworth; Trevor Howe; Kilian V M Huber; Jian Jin; Stefan Knapp; Joanne D Kotz; Ryan G Kruger; Derek Lowe; Mary M Mader; Brian Marsden; Anke Mueller-Fahrnow; Susanne Müller; Ronan C O'Hagan; John P Overington; Dafydd R Owen; Saul H Rosenberg; Bryan Roth; Brian Roth; Ruth Ross; Matthieu Schapira; Stuart L Schreiber; Brian Shoichet; Michael Sundström; Giulio Superti-Furga; Jack Taunton; Leticia Toledo-Sherman; Chris Walpole; Michael A Walters; Timothy M Willson; Paul Workman; Robert N Young; William J Zuercher
Journal:  Nat Chem Biol       Date:  2015-08       Impact factor: 15.040
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  5 in total

1.  Targeting mTOR by CZ415 Suppresses Cell Proliferation and Promotes Apoptosis via Lipin-1 in Cervical Cancer In Vitro and In Vivo.

Authors:  Jinfeng Zhang
Journal:  Reprod Sci       Date:  2020-09-17       Impact factor: 3.060

2.  Discovery of GSK8612, a Highly Selective and Potent TBK1 Inhibitor.

Authors:  Douglas W Thomson; Daniel Poeckel; Nico Zinn; Christina Rau; Katrin Strohmer; Anne J Wagner; Alan P Graves; Jessica Perrin; Marcus Bantscheff; Birgit Duempelfeld; Viera Kasparcova; Joshi M Ramanjulu; G Scott Pesiridis; Marcel Muelbaier; Giovanna Bergamini
Journal:  ACS Med Chem Lett       Date:  2019-03-11       Impact factor: 4.345

3.  A high content, phenotypic 'scar-in-a-jar' assay for rapid quantification of collagen fibrillogenesis using disease-derived pulmonary fibroblasts.

Authors:  Robert B Good; Jessica D Eley; Elaine Gower; Genevieve Butt; Andrew D Blanchard; Andrew J Fisher; Carmel B Nanthakumar
Journal:  BMC Biomed Eng       Date:  2019-06-28

4.  ERK inhibition sensitizes CZ415-induced anti-osteosarcoma activity in vitro and in vivo.

Authors:  Gang Yin; Jin Fan; Wei Zhou; Qingfeng Ding; Jun Zhang; Xuan Wu; Pengyu Tang; Hao Zhou; Bowen Wan; Guoyong Yin
Journal:  Oncotarget       Date:  2017-05-30

Review 5.  Overview of Research into mTOR Inhibitors.

Authors:  Beibei Mao; Qi Zhang; Li Ma; Dong-Sheng Zhao; Pan Zhao; Peizheng Yan
Journal:  Molecules       Date:  2022-08-19       Impact factor: 4.927
  5 in total

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