title: Discovery of a Novel Scaffold as an Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Based on the Pyrrolopiperazinone Alkaloid, Longamide B.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.|Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi, Osaka, 560-0043, Japan.
authors.forename: Zenyu
authors.initials: Z
authors.lastname: Shiokawa
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Kashiwabara
authors.affiliation: Schrödinger K.K., 17F Marunouchi Trust Tower North, 1-8-1 Marunouchi Chiyoda-ku, Tokyo, 100-0005, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshidome
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka-shi, Osaka, 560-0043, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Fukase
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Inuki
authors.affiliation: Department of Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Fujimoto
mesh_terms: D055808:Drug Discovery; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D045170:Matrix Attachment Regions; D008958:Models, Molecular; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D010879:Piperazines; D011720:Pyrazoles; D011758:Pyrroles; C511002:longamide B; C518524:pyrazolopiperazinone
keywords: docking models; hanishin; indoleamine 2,3-dioxygenase 1; longamide B; piperazinones