Discovery and Preclinical Evaluation of BMS-986242, a Potent, Selective Inhibitor of Indoleamine-2,3-dioxygenase 1
| Autor: | Steven P. Seitz, Gregory D. Vite, John T. Hunt, Mark Fereshteh, Cherney Emily Charlotte, Joseph Fargnoli, Lorell Discenza, Liping Zhang, Jennifer Brown, Xin Li, Kevin Stefanski, Christine Huang, Asoka Ranasinghe, Lisa M. Kopcho, Xiao Zhu, Aaron Balog, Diane Delpy, Sarah C. Traeger, Jesse Swanson, Mary F. Grubb, Zheng Yang, Theresa Ziemba, Kathy A. Johnston, Kimberly A. Foster, Johnni Gullo-Brown, Celia D’Arienzo, Susheel Jethanand Nara, Robert M. Borzilleri, Derrick Maley, Tai-An Lin |
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| Rok vydání: | 2020 |
| Předmět: |
010405 organic chemistry
business.industry medicine.medical_treatment Organic Chemistry Cancer medicine.disease 01 natural sciences Biochemistry In vitro 0104 chemical sciences 010404 medicinal & biomolecular chemistry Immune system Cancer immunotherapy In vivo Renal cell carcinoma Dioxygenase Drug Discovery medicine Cancer research Indoleamine 2 3-dioxygenase business |
| Zdroj: | ACS Med Chem Lett |
| ISSN: | 1948-5875 |
| Popis: | [Image: see text] 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. |
| Databáze: | OpenAIRE |
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