UA62784, a novel inhibitor of centromere protein E kinesin-like protein.
UA62784, a novel inhibitor of centromere protein E kinesin-like protein.
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DOI：
10.1158/1535-7163.mct-08-0789
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发表时间：
2009-01
影响因子：
5.7
通讯作者：
Von Hoff DD
中科院分区：
文献类型：
--
作者：
Henderson MC;Shaw YJ;Wang H;Han H;Hurley LH;Flynn G;Dorr RT;Von Hoff DD
胰腺癌是癌症死亡的第四大原因。需要新的靶点和治疗选择来帮助治疗胰腺癌。化合物UA 62784是一种新的芴酮，对CENP-E驱动蛋白样蛋白具有抑制活性。UA 62784由于其在缺失DPC 4基因的同基因胰腺癌细胞系中的选择性而被分离。UA 62784可能通过抑制CENP-E的微管相关ATP酶活性，通过抑制中期板的染色体聚集，导致有丝分裂停滞。此外，CENP-E在有丝分裂期间与动粒的结合不受UA 62784的影响，这表明靶点位于CENP-E的运动结构域内。UA 62784是一种新的CENP-E特异性抑制剂，其活性提示抗有丝分裂药物在治疗胰腺癌中的潜在作用。
Pancreatic carcinoma is the fourth-leading cause of death from cancer. Novel targets and therapeutic options are needed to aid in the treatment of pancreatic cancer. The compound UA62784 is a novel fluorenone with inhibitory activity against the CENP-E kinesin-like protein. UA62784 was isolated due to its selectivity in isogenic pancreatic carcinoma cell lines with a deletion of the DPC4 gene. UA62784 causes mitotic arrest by inhibiting chromosome congression at the metaphase plate, likely through inhibition of the microtubule-associated ATPase activity of CENP-E. Furthermore, CENP-E binding to kinetochores during mitosis is not affected by UA62784, suggesting that the target lies within the motor domain of CENP-E. UA62784 is a novel specific inhibitor of CENP-E and its activity suggests a potential role for antimitotic drugs in treating pancreatic carcinomas.