LY-3381916 is a potent, selective and brain-penetrant Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor with IC50 of 7 nM.
LY-3381916 displays no significant inhibitory activity against TDO2 (IC50>20 uM), shows no confounding agonism of AHR up to 100 uM.
LY3381916 occupies the heme-binding pocket of IDO1, binds to newly synthesized apo-IDO1 lacking heme, but does not inhibit mature heme-bound IDO1.
LY-3381916 exhibits substantial inhibition of IDO1 in tumors requires the turn-over of mature heme-bound IDO1.
LY-3381916 enhances anti-PD-L1 antibody (LY3300054) activity in pre-clinical tumor model.
