Literature DB >> 33603977

Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1.

Emily C Cherney1, Liping Zhang1, Susheel Nara2, Xiao Zhu1, Johnni Gullo-Brown1, Derrick Maley1, Tai-An Lin1, John T Hunt1, Christine Huang1, Zheng Yang1, Celia Darienzo1, Lorell Discenza1, Asoka Ranasinghe1, Mary Grubb1, Theresa Ziemba1, Sarah C Traeger1, Xin Li1, Kathy Johnston1, Lisa Kopcho1, Mark Fereshteh1, Kimberly Foster1, Kevin Stefanski1, Joseph Fargnoli1, Jesse Swanson1, Jennifer Brown1, Diane Delpy1, Steven P Seitz1, Robert Borzilleri1, Gregory Vite1, Aaron Balog1.   

Abstract

Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing dioxygenase enzyme implicated in cancer immune response. This account details the discovery of BMS-986242, a novel IDO1 inhibitor designed for the treatment of a variety of cancers including metastatic melanoma and renal cell carcinoma. Given the substantial interest around this target for cancer immunotherapy, we sought to identify a structurally differentiated clinical candidate that performs comparably to linrodostat (BMS-986205) in terms of both in vitro potency and in vivo pharmacodynamic effect in a mouse xenograft model. On the basis of its preclinical profile, BMS-986242 was selected as a candidate for clinical development.
© 2021 American Chemical Society.

Entities:  

Year:  2021        PMID： 33603977      PMCID： PMC7883469          DOI： 10.1021/acsmedchemlett.0c00668

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


  46 in total

1.  Indoleamine 2,3-dioxygenase serves as a marker of poor prognosis in gene expression profiles of serous ovarian cancer cells.

Authors:  Aikou Okamoto; Takashi Nikaido; Kazunori Ochiai; Satoshi Takakura; Misato Saito; Yuko Aoki; Nobuya Ishii; Nozomu Yanaihara; Kyosuke Yamada; Osamu Takikawa; Rie Kawaguchi; Seiji Isonishi; Tadao Tanaka; Mitsuyoshi Urashima
Journal:  Clin Cancer Res       Date:  2005-08-15       Impact factor: 12.531

Review 2.  Challenges in the Discovery of Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors.

Authors:  Ute F Röhrig; Somi Reddy Majjigapu; Pierre Vogel; Vincent Zoete; Olivier Michielin
Journal:  J Med Chem       Date:  2015-05-26       Impact factor: 7.446

3.  Preclinical Characterization of Linrodostat Mesylate, a Novel, Potent, and Selective Oral Indoleamine 2,3-Dioxygenase 1 Inhibitor.

Authors:  Aaron Balog; Tai-An Lin; Derrick Maley; Johnni Gullo-Brown; Enzo Hamza Kandoussi; Jianing Zeng; John T Hunt
Journal:  Mol Cancer Ther       Date:  2020-12-09       Impact factor: 6.261

4.  The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor zeta-chain and induce a regulatory phenotype in naive T cells.

Authors:  Francesca Fallarino; Ursula Grohmann; Sylvaine You; Barbara C McGrath; Douglas R Cavener; Carmine Vacca; Ciriana Orabona; Roberta Bianchi; Maria L Belladonna; Claudia Volpi; Pere Santamaria; Maria C Fioretti; Paolo Puccetti
Journal:  J Immunol       Date:  2006-06-01       Impact factor: 5.422

5.  GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase.

Authors:  David H Munn; Madhav D Sharma; Babak Baban; Heather P Harding; Yuhong Zhang; David Ron; Andrew L Mellor
Journal:  Immunity       Date:  2005-05       Impact factor: 31.745

Review 6.  Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway.

Authors:  Amy B Dounay; Jamison B Tuttle; Patrick R Verhoest
Journal:  J Med Chem       Date:  2015-08-05       Impact factor: 7.446

7.  CTLA-4-Ig regulates tryptophan catabolism in vivo.

Authors:  Ursula Grohmann; Ciriana Orabona; Francesca Fallarino; Carmine Vacca; Filippo Calcinaro; Alberto Falorni; Paola Candeloro; Maria L Belladonna; Roberta Bianchi; Maria C Fioretti; Paolo Puccetti
Journal:  Nat Immunol       Date:  2002-09-30       Impact factor: 25.606

8.  A TDO2-AhR signaling axis facilitates anoikis resistance and metastasis in triple-negative breast cancer.

Authors:  Nicholas C D'Amato; Thomas J Rogers; Michael A Gordon; Lisa I Greene; Dawn R Cochrane; Nicole S Spoelstra; Travis G Nemkov; Angelo D'Alessandro; Kirk C Hansen; Jennifer K Richer
Journal:  Cancer Res       Date:  2015-09-11       Impact factor: 12.701

9.  Mapping the Binding Trajectory of a Suicide Inhibitor in Human Indoleamine 2,3-Dioxygenase 1.

Authors:  Khoa N Pham; Syun-Ru Yeh
Journal:  J Am Chem Soc       Date:  2018-10-24       Impact factor: 15.419

10.  IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan.

Authors:  Richard Metz; Sonja Rust; James B Duhadaway; Mario R Mautino; David H Munn; Nicholas N Vahanian; Charles J Link; George C Prendergast
Journal:  Oncoimmunology       Date:  2012-12-01       Impact factor: 8.110
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  3 in total

1.  Discovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy.

Authors:  Liping Zhang; Emily C Cherney; Xiao Zhu; Tai-An Lin; Johnni Gullo-Brown; Derrick Maley; Kathy Johnston-Allegretto; Lisa Kopcho; Mark Fereshteh; Christine Huang; Xin Li; Sarah C Traeger; Gopal Dhar; Aravind Anandam; Sandeep Mahankali; Shweta Padmanabhan; Prabhakar Rajanna; Venkata Murali; Thanga Mariappan; Robert Borzilleri; Gregory Vite; John T Hunt; Aaron Balog
Journal:  ACS Med Chem Lett       Date:  2021-03-02       Impact factor: 4.345

2.  Conformational-Analysis-Guided Discovery of 2,3-Disubstituted Pyridine IDO1 Inhibitors.

Authors:  Emily C Cherney; Liping Zhang; Weiwei Guo; Audris Huang; David Williams; Steven Seitz; Weifang Shan; Xiao Zhu; Johnni Gullo-Brown; Derrick Maley; Tai-An Lin; John T Hunt; Christine Huang; Zheng Yang; Celia J D'Arienzo; Lorell N Discenza; Asoka Ranasinghe; Mary F Grubb; Sarah C Traeger; Xin Li; Kathy A Johnston; Lisa Kopcho; Mark Fereshteh; Kimberly A Foster; Kevin Stefanski; Diane Delpy; Gopal Dhar; Aravind Anandam; Sandeep Mahankali; Shweta Padmanabhan; Prabhakar Rajanna; Venkata Murali; T Thanga Mariappan; Shabeerali Pattasseri; Roshan Y Nimje; Zhenqiu Hong; James Kempson; Richard Rampulla; Arvind Mathur; Anuradha Gupta; Robert Borzilleri; Gregory Vite; Aaron Balog
Journal:  ACS Med Chem Lett       Date:  2021-06-16       Impact factor: 4.632

Review 3.  Kynurenines as a Novel Target for the Treatment of Malignancies.

Authors:  Adrian Mor; Anna Tankiewicz-Kwedlo; Dariusz Pawlak
Journal:  Pharmaceuticals (Basel)       Date:  2021-06-23
  3 in total

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