Motolimod

Motolimod (VTX-2337;VTX-378) is a selective Toll-like receptor 8 (TLR8) agonist, with an EC₅₀ of approximately 100 nM. IC50 & Target: EC50: 100 nM (TLR8)^[1] In Vitro: Among the TLRs tested (TLR2, 3, 4, 5, 7, 8, and 9), Motolimod (VTX-2337) selectively activates TLR8. Motolimod stimulates the production of both TNFα (EC₅₀=140±30 nM based on 10 donors) and IL-12 (EC₅₀=120±30 nM based on 10 donors) in PBMCs. The EC₅₀ value for MIP-1β induction is 60 nM for Motolimod^[1]. In Vivo: Monkeys receive a subcutaneous injection of Motolimod (1 or 10 mg/kg), and plasma is collected predose, 6, 12, 24, and 96 h post-injection. For the 10 mg/kg dose, mean plasma levels of IL-1β increase from baseline levels of 0.5 pg/mL, up to 9.12±2.7 ng/mL (p<0.05, t-test) at 6 h post-administration of Motolimod (10 mg/kg). Circulating levels of IL-18 also increase from a baseline of ~ 1 pg/mL to 68.7±4.4 pg/mL (p<0.05, t-test) at 6 h in response to the Motolimod (VTX-2337) treatment (10 mg/kg). Levels of IL-6 are monitored, as this mediator is induced in response to TLR8 activation, but the release is independent of NLRP3 inflammasome activation. In addition, plasma levels of IFNγ are assessed as a measure of NK cell activation in response to Motolimod treatment^[2].