121st General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Event Hall
Time 4월 19일 (목요일) 11:00~12:30
Code MEDI.P-640
Subject Synthesis and Molecular Modeling Studies of N`-Hydroxyindazolecarboximidamides as Novel Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors
Authors AhRa Go, HEE NANG CHOI, Jong Yeon Hwang*, Hyunjin Kim1, jae du ha2
Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Korea
1Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Korea
2WCI, Korea Research Institute of Chemical Technology, Korea
Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that is highly overexpressed in various cancer cells and antigen-presenting cells. It has emerged as an attractive therapeutic target for cancer immunotherapy, which has prompted high interest in the development of small-molecule inhibitors. To discover novel IDO1 inhibitors, we designed and synthesized a series of N0-hydroxyindazolecarboximidamides. Among the compounds synthesized, compound 8a inhibited both tryptophan depletion and kynurenine production through the IDO1 enzyme. Molecular docking studies revealed that 8a binds to IDO1 with the same binding mode as the analog, epacadostat (INCB24360). Here, we report the synthesis and biological evaluation of these hydroxyindazolecarboximidamides and present the molecular docking study of 8a with IDO1.
E-mail rhrkfk@hanmail.net