Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation.

ABSTRACT: With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and

SUBMITTER: Xu X 

PROVIDER: S-EPMC6327983 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature