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

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

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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