Zhang Liping, Cherney Emily C, Zhu Xiao, Lin Tai-An, Gullo-Brown Johnni, Maley Derrick, Johnston-Allegretto Kathy, Kopcho Lisa, Fereshteh Mark, Huang Christine, Li Xin, Traeger Sarah C, Dhar Gopal, Anandam Aravind, Mahankali Sandeep, Padmanabhan Shweta, Rajanna Prabhakar, Murali Venkata, Mariappan Thanga, Borzilleri Robert, Vite Gregory, Hunt John T, Balog Aaron
Bristol Myers Squibb Research and Development, Princeton, New Jersey 08543-4000, United States.
Biocon Bristol Myers Squibb R&D Center, Biocon Park, Jigani Link Road, Bengaluru, Karnataka 560099, India.
ACS Med Chem Lett. 2021 Mar 2;12(3):494-501. doi: 10.1021/acsmedchemlett.1c00014. eCollection 2021 Mar 11.
Indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as a target for small-molecule immunotherapy for the treatment of a variety of cancers including renal cell carcinoma and metastatic melanoma. This work focuses on the identification of IDO1 inhibitors containing replacements or isosteres for the amide found in BMS-986205, an amide-containing, IDO1-selective inhibitor currently in phase III clinical trials. Detailed subsequently are efforts to identify a structurally differentiated IDO1 inhibitor via the pursuit of a variety of heterocyclic isosteres, leading to the discovery of highly potent, imidazopyridine-containing IDO1 inhibitors.
吲哚胺2,3-双加氧酶1（IDO1）已被确定为小分子免疫疗法的靶点，用于治疗包括肾细胞癌和转移性黑色素瘤在内的多种癌症。这项工作的重点是鉴定IDO1抑制剂，这些抑制剂含有BMS-986205中酰胺的替代物或电子等排体，BMS-986205是一种含酰胺的IDO1选择性抑制剂，目前正处于III期临床试验阶段。随后详细介绍了通过研究多种杂环电子等排体来鉴定结构上有差异的IDO1抑制剂的工作，从而发现了高效的含咪唑并吡啶的IDO1抑制剂。
