vx 497

VX-148 is a novel, non-competitive IMPDH inhibitor with a K(i) value of 6 nM for IMPDH Type II enzyme. It is slightly more effective than mycophenolic acid and VX-497 in inhibiting the proliferation of primary human lymphocytes (IC(50) approximately 80 nM). The presence of exogenous guanosine can mitigate VX-148's inhibitory activity. Notably, VX-148 does not impede the proliferation of non-lymphocyte types such as fibroblasts, indicating selective inhibition of IMPDH activity. The compound exhibits oral bioavailability in rats and mice; oral administration of VX-148 inhibits the primary antibody response in mice in a dose-dependent manner, with an ED(50) of 38 mg kg b.i.d. Additionally, in mice, VX-148 at a dosage of 100 mg kg b.i.d. significantly prolongs skin graft survival time.

Merimepodib (VX-497) is a novel, noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH).