Identification of Type 1 Inosine Monophosphate Dehydrogenase as an Antiangiogenic Drug Target

To rapidly discover clinically useful angiogenesis inhibitors, we created and screened a library of existing drugs for inhibition of endothelial cell proliferation. Mycophenolic acid (MPA), an immunosuppressive drug, was found to potently inhibit endothelial cell proliferation in vitro and block tumor-induced angiogenesis in vivo. Using RNA interference, we found that knockdown of one of the two known isoforms of inosine monophosphate dehydrogenase (IMPDH-1) is sufficient to cause endothelial cell cycle arrest.