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

  • ACS Med Chem Lett. 2021 Jan 28;12(2):288-294. doi: 10.1021/acsmedchemlett.0c00668.
Emily C Cherney  1 ,  Liping Zhang  1 ,  Susheel Nara  2 ,  Xiao Zhu  1 ,  Johnni Gullo-Brown  1 ,  Derrick Maley  1 ,  Tai-An Lin  1 ,  John T Hunt  1 ,  Christine Huang  1 ,  Zheng Yang  1 ,  Celia Darienzo  1 ,  Lorell Discenza  1 ,  Asoka Ranasinghe  1 ,  Mary Grubb  1 ,  Theresa Ziemba  1 ,  Sarah C Traeger  1 ,  Xin Li  1 ,  Kathy Johnston  1 ,  Lisa Kopcho  1 ,  Mark Fereshteh  1 ,  Kimberly Foster  1 ,  Kevin Stefanski  1 ,  Joseph Fargnoli  1 ,  Jesse Swanson  1 ,  Jennifer Brown  1 ,  Diane Delpy  1 ,  Steven P Seitz  1 ,  Robert Borzilleri  1 ,  Gregory Vite  1 ,  Aaron Balog  1
Affiliations
  • 1. Bristol Myers Squibb Research and Development, 3551 Lawrenceville, Princeton Rd, Lawrence Township, New Jersey 08648, United States.
  • 2. Biocon BMS R&D Center, Bommasandra Jigani Link Rd, Bommasandra Industrial Area, Bengaluru, Karnataka 560099, India.
PMID: 33603977 DOI: 10.1021/acsmedchemlett.0c00668
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.

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