VX-148

VX-148 is a second-generation, orally administered small molecule inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that catalyzes the rate-limiting step in the de novo biosynthesis of guanine nucleotides. By inhibiting IMPDH—particularly type II isoform—VX-148 selectively impairs lymphocyte proliferation due to their reliance on this pathway for nucleotide synthesis. This mechanism underlies its immunosuppressive effects and potential utility in treating autoimmune diseases and preventing transplant rejection. VX-148 demonstrated greater potency than mycophenolic acid in preclinical studies and showed selectivity for lymphocytes over nonlymphoid cells. The drug was developed by Vertex Pharmaceuticals but has been discontinued after reaching phase 2 clinical trials for indications including psoriasis, transplant rejection, and viral infections[1][2][3][4][5][6].