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Discovery of a Novel Scaffold as an Indoleamine 2,3‐Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B
Author(s) -
Shiokawa Zenyu,
Kashiwabara Emi,
Yoshidome Daisuke,
Fukase Koichi,
Inuki Shinsuke,
Fujimoto Yukari
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600446
Subject(s) - indoleamine 2,3 dioxygenase , chemistry , alkaloid , thioamide , docking (animal) , immune system , tryptophan , scaffold , stereochemistry , drug discovery , kynurenine , pharmacology , biochemistry , biology , medicine , immunology , nursing , amino acid , biomedical engineering
Indoleamine 2,3‐dioxygenase 1 (IDO1) has emerged as a key target for cancer therapy, as IDO1 plays a critical role in the capacity of tumor cells to evade the immune system. The pyrrolopiperazinone alkaloid longamide B and its derivatives were identified as novel IDO1 inhibitors based on docking studies and small library synthesis. The thioamide derivative showed higher IDO1 inhibitory activity than longamide B, and displayed an activity similar to that of a representative IDO1 inhibitor, 1‐methyl‐tryptophan. These results suggest that the pyrrolopiperazinone scaffold of longamide B could be used in the development of IDO1 inhibitors.