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.
Chong
Curtis R
CR
Department of Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Qian
David Z
DZ
Pan
Fan
F
Wei
Yongfeng
Y
Pili
Roberto
R
Sullivan
David J
DJ
Liu
Jun O
JO
D020533:Angiogenesis Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D009173:Mycophenolic Acid / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000098:blood supply / Q000473:pathology; D034622:RNA Interference; D014470:Umbilical Cord / Q000187:drug effects
D020533:Angiogenesis Inhibitors; D004791:Enzyme Inhibitors; D007168:IMP Dehydrogenase; D009173:Mycophenolic Acid