LM10

LM10 is a potent and selective small molecule inhibitor of tryptophan 2,3-dioxygenase (TDO), an enzyme that degrades tryptophan along the kynurenine pathway to promote tumoral immune resistance. Developed as part of a medicinal chemistry program at the Université Catholique de Louvain to improve upon the poor bioavailability of earlier inhibitors like 680C91, LM10 features a 6-fluoro-indole scaffold with a tetrazolyl-vinyl side chain. It acts as a competitive inhibitor of TDO (Ki = 5.6 μM) without inhibiting indoleamine 2,3-dioxygenase (IDO). In preclinical models, systemic administration of LM10 restored the ability of the immune system to reject TDO-expressing tumors by preventing local tryptophan depletion and kynurenine accumulation, which otherwise suppress T-cell proliferation and activity.

Other names

trans-6-Fluoro-3-[2-(1H-tetrazol-5-yl)vinyl]-1H-indole