Wills Veronica S, Allen Cheryl, Holstein Sarah A, Wiemer David F
Department of Chemistry, University of Iowa , Iowa City, Iowa 52242-1294, United States.
Department of Medicine, Roswell Park Cancer Institute , Buffalo, New York 14263, United States.
ACS Med Chem Lett. 2015 Oct 28;6(12):1195-8. doi: 10.1021/acsmedchemlett.5b00334. eCollection 2015 Dec 10.
Studies of triazole bisphosphonates have resulted in identification of a potent inhibitor of geranylgeranyl diphosphate synthase (IC50 = 45 nM) with very good selectivity for this enzyme over farnesyl diphosphate synthase (IC50 = 28 μM). This compound also potently disrupts geranylgeranylation and induces cytotoxicity in human myeloma cells at submicromolar levels, suggesting that it may serve as a lead compound for treatment of malignancies characterized by excessive protein secretion.
对三唑双膦酸盐的研究已鉴定出一种香叶基香叶基二磷酸合酶的强效抑制剂（IC50 = 45 nM），与法尼基二磷酸合酶相比，该抑制剂对这种酶具有非常好的选择性（IC50 = 28 μM）。该化合物在亚微摩尔水平下还能有效破坏香叶基香叶基化并诱导人骨髓瘤细胞的细胞毒性，这表明它可能作为一种先导化合物用于治疗以蛋白质过度分泌为特征的恶性肿瘤。
