Chong Curtis R, Qian David Z, Pan Fan, Wei Yongfeng, Pili Roberto, Sullivan David J, Liu Jun O
Department of Pharmacology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Med Chem. 2006 May 4;49(9):2677-80. doi: 10.1021/jm051225t.
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.
为了快速发现临床上有用的血管生成抑制剂，我们创建并筛选了一个现有药物库，以寻找能够抑制内皮细胞增殖的药物。霉酚酸（MPA），一种免疫抑制药物，被发现能够在体外有效抑制内皮细胞增殖，并在体内阻断肿瘤诱导的血管生成。通过RNA干扰，我们发现敲低肌苷单磷酸脱氢酶（IMPDH-1）两种已知亚型之一就足以导致内皮细胞周期停滞。
