Open AccessDiscovery of Imidazopyridines as Potent Inhibitors of Indoleamine 2,3-Dioxygenase 1 for Cancer Immunotherapy
Author(s) -
Liping Zhang,
Emily C. Cherney,
Xiaohan Zhu,
Tai-An Lin,
Johnni Gullo-Brown,
Derrick Maley,
Kathy Johnston-Allegretto,
Lisa M. Kopcho,
Mark Fereshteh,
Christine Huang,
Xin Li,
Sarah C. Traeger,
Gopal Dhar,
Aravind Anandam,
Sandeep Mahankali,
Shweta Padmanabhan,
Prabhakar Rajanna,
Venkata Murali,
T. Thanga Mariappan,
R. M. Borzilleri,
Gregory D. Vite,
John T. Hunt,
Aaron Balog
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.1c00014
Subject(s) - indoleamine 2,3 dioxygenase , immunotherapy , amide , cancer , medicine , chemistry , pharmacology , computational biology , biology , biochemistry , tryptophan , amino acid
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.