IMPDH2 Inhibitors

The chemical class of IMPDH2 inhibitors encompasses a range of compounds that are primarily utilized for their immunosuppressive and antiviral properties. These inhibitors target the IMPDH2 enzyme, which is essential for the synthesis of guanine nucleotides, thereby affecting lymphocyte proliferation and immune response. Mycophenolic Acid and its prodrug, Mycophenolate Mofetil, are among the most well-known inhibitors of IMPDH2. They act by binding to the NAD+ site of IMPDH2, effectively reducing the synthesis of guanine nucleotides, which are vital for DNA and RNA synthesis. This mechanism of action is pivotal in suppressing immune responses, particularly in the context of organ transplantation. Similarly, Mizoribine and Merimepodib function by inhibiting IMPDH2, thereby exerting immunosuppressive effects.

Other compounds such as Ribavirin, Tiazofurin, and Benzamide Riboside inhibit IMPDH2 by mimicking its natural substrates. Ribavirin, for instance, is a structural analogue of inosine monophosphate and inhibits IMPDH2, leading to antiviral effects alongside its immunosuppressive action. Tiazofurin is metabolized into an active form that inhibits IMPDH2, affecting nucleotide synthesis.Additionally, compounds like VX-497 and AVN-944 are potent inhibitors of IMPDH2, specifically designed to reduce guanine nucleotide synthesis and lymphocyte proliferation. While Leflunomide and Brequinar primarily target other enzymes, they also exhibit inhibitory effects on IMPDH2, contributing to their immunomodulatory actions. Sildenafil, although known for its phosphodiesterase inhibiting activity, has been shown to inhibit IMPDH2 at higher concentrations.