Literature DB >> 30429955

Discovery of 4-Azaindole Inhibitors of TGFβRI as Immuno-oncology Agents.

Yong Zhang1, Yufen Zhao1, Andrew J Tebben1, Steven Sheriff1, Max Ruzanov1, Mark P Fereshteh1, Yi Fan1, Jonathan Lippy1, Jesse Swanson1, Ching-Ping Ho1, Barri S Wautlet1, Anne Rose1, Karen Parrish1, Zheng Yang1, Andrew F Donnell1, Liping Zhang1, Brian E Fink1, Gregory D Vite1, Karen Augustine-Rauch1, Joseph Fargnoli1, Robert M Borzilleri1.   

Abstract

The multifunctional cytokine TGFβ plays a central role in regulating antitumor immunity. It has been postulated that inhibition of TGFβ signaling in concert with checkpoint blockade will provide improved and durable immune response against tumors. Herein, we describe a novel series of 4-azaindole TGFβ receptor kinase inhibitors with excellent selectivity for TGFβ receptor 1 kinase. The combination of compound 3f and an antimouse-PD-1 antibody demonstrated significantly improved antitumor efficacy compared to either treatment alone in a murine tumor model.

Entities:  

Year:  2018        PMID： 30429955      PMCID： PMC6231184          DOI： 10.1021/acsmedchemlett.8b00357

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


  27 in total

1.  Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis.

Authors:  Anne-Charlotte de Gouville; Valerie Boullay; Gael Krysa; Julia Pilot; Jean-Marie Brusq; Florence Loriolle; Jean-Michel Gauthier; Stephen A Papworth; Alain Laroze; Françoise Gellibert; Stephane Huet
Journal:  Br J Pharmacol       Date:  2005-05       Impact factor: 8.739

2.  Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis.

Authors:  Eugene T Grygielko; William M Martin; Christopher Tweed; Peter Thornton; John Harling; David P Brooks; Nicholas J Laping
Journal:  J Pharmacol Exp Ther       Date:  2005-03-15       Impact factor: 4.030

Review 3.  How cells read TGF-beta signals.

Authors:  J Massagué
Journal:  Nat Rev Mol Cell Biol       Date:  2000-12       Impact factor: 94.444

4.  Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent.

Authors:  Cheng Hua Jin; Maddeboina Krishnaiah; Domalapally Sreenu; Vura B Subrahmanyam; Kota S Rao; Hwa Jeong Lee; So-Jung Park; Hyun-Ju Park; Kiho Lee; Yhun Yhong Sheen; Dae-Kee Kim
Journal:  J Med Chem       Date:  2014-05-13       Impact factor: 7.446

5.  Learning from PD-1 Resistance: New Combination Strategies.

Authors:  Xia Bu; Kathleen M Mahoney; Gordon J Freeman
Journal:  Trends Mol Med       Date:  2016-05-09       Impact factor: 11.951

6.  Transforming growth factor-beta receptor type 1 (TGFbetaRI) kinase activity but not p38 activation is required for TGFbetaRI-induced myofibroblast differentiation and profibrotic gene expression.

Authors:  Ann M Kapoun; Nicholas J Gaspar; Ying Wang; Debby Damm; Yu-Wang Liu; Gilbert O'young; Diana Quon; Andrew Lam; Kimberly Munson; Thomas-Toan Tran; Jing Ying Ma; Alison Murphy; Sundeep Dugar; Sarvajit Chakravarty; Andrew A Protter; Fu-Qiang Wen; Xiangde Liu; Stephen I Rennard; Linda Slanec Higgins
Journal:  Mol Pharmacol       Date:  2006-05-17       Impact factor: 4.436

7.  Dihydropyrrolopyrazole transforming growth factor-beta type I receptor kinase domain inhibitors: a novel benzimidazole series with selectivity versus transforming growth factor-beta type II receptor kinase and mixed lineage kinase-7.

Authors:  Hong-yu Li; Yan Wang; Charles R Heap; Chi-Hsin R King; Sreenivasa R Mundla; Matthew Voss; David K Clawson; Lei Yan; Robert M Campbell; Bryan D Anderson; Jill R Wagner; Karen Britt; Ku X Lu; William T McMillen; Jonathan M Yingling
Journal:  J Med Chem       Date:  2006-03-23       Impact factor: 7.446

Review 8.  Combination cancer immunotherapy and new immunomodulatory targets.

Authors:  Kathleen M Mahoney; Paul D Rennert; Gordon J Freeman
Journal:  Nat Rev Drug Discov       Date:  2015-08       Impact factor: 84.694

Review 9.  Targeting the TGFβ signalling pathway in disease.

Authors:  Rosemary J Akhurst; Akiko Hata
Journal:  Nat Rev Drug Discov       Date:  2012-09-24       Impact factor: 84.694

10.  Rapid generation of a high quality lead for transforming growth factor-beta (TGF-beta) type I receptor (ALK5).

Authors:  Frederick W Goldberg; Richard A Ward; Steven J Powell; Judit E Debreczeni; Richard A Norman; Nicola J Roberts; Allan P Dishington; Helen J Gingell; Kate F Wickson; Andrew L Roberts
Journal:  J Med Chem       Date:  2009-12-10       Impact factor: 7.446
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  4 in total

1.  Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors.

Authors:  Wangyang Tu; Fanglong Yang; Guoji Xu; Jiangtao Chi; Zhiwei Liu; Wei Peng; Bing Hu; Lei Zhang; Hong Wan; Nan Yu; Fangfang Jin; Qiyue Hu; Lianshan Zhang; Feng He; Weikang Tao
Journal:  ACS Med Chem Lett       Date:  2019-06-03       Impact factor: 4.345

2.  Discovery of BMS-986260, a Potent, Selective, and Orally Bioavailable TGFβR1 Inhibitor as an Immuno-oncology Agent.

Authors:  Upender Velaparthi; Chetan Padmakar Darne; Jayakumar Warrier; Peiying Liu; Hasibur Rahaman; Karen Augustine-Rauch; Karen Parrish; Zheng Yang; Jesse Swanson; Jennifer Brown; Gopal Dhar; Aravind Anandam; Vinay K Holenarsipur; Kamalavenkatesh Palanisamy; Barri S Wautlet; Mark P Fereshteh; Jonathan Lippy; Andrew J Tebben; Steven Sheriff; Max Ruzanov; Chunhong Yan; Anuradha Gupta; Arun Kumar Gupta; Muthalagu Vetrichelvan; Arvind Mathur; Marina Gelman; Rajinder Singh; Todd Kinsella; Anwar Murtaza; Joseph Fargnoli; Gregory Vite; Robert M Borzilleri
Journal:  ACS Med Chem Lett       Date:  2020-01-28       Impact factor: 4.345

3.  Structural biology of the TGFβ family.

Authors:  Erich J Goebel; Kaitlin N Hart; Jason C McCoy; Thomas B Thompson
Journal:  Exp Biol Med (Maywood)       Date:  2019-10-09

4.  TGFβ2 and TGFβ3 mediate appropriate context-dependent phenotype of rat valvular interstitial cells.

Authors:  Faye Wang; Cindy Zhang; Jae Kwagh; Brian Strassle; Jinqing Li; Minxue Huang; Yunling Song; Brenda Lehman; Richard Westhouse; Kamalavenkatesh Palanisamy; Vinay K Holenarsipur; Robert Borzilleri; Karen Augustine-Rauch
Journal:  iScience       Date:  2021-02-03
  4 in total

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