Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors (Retracted Article. See vol 298, pg 2327, 2002)
Prevention of chemotherapy-induced alopecia in rats by CDK inhibitors (Retracted Article. See vol 298, pg 2327, 2002)
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DOI：
10.1126/science.291.5501.134
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发表时间：
2001-01-05
期刊：
影响因子：
56.9
通讯作者：
Kuyper, LF
中科院分区：
文献类型：
--
作者：
Davis, ST;Benson, BG;Kuyper, LF
大多数传统的细胞毒性抗癌药物会消融快速分裂的毛囊上皮并诱发脱发（脱发）。细胞周期蛋白依赖性激酶 2 (CDK2) 是真核细胞周期进展的正调节因子，其抑制可能是通过阻止细胞周期并降低上皮细胞对许多细胞周期活性抗肿瘤药物的敏感性来预防化疗引起的脱发 (CIA) 的治疗策略。使用基于结构的方法开发了有效的 CDK2 小分子抑制剂。在 CIA 新生大鼠模型中局部施用这些化合物可减少 33% 至 50% 动物施用部位的脱发。因此，抑制 CDK2 代表了预防癌症患者 CIA 的潜在有用方法。
Most traditional cytotoxic anticancer agents ablate the rapidly dividing epithelium of the hair follicle and induce alopecia (hair Loss). Inhibition of cyclin-dependent kinase 2 (CDK2), a positive regulator of eukaryotic cell cycle progression, may represent a therapeutic strategy for prevention of chemotherapy-induced alopecia (CIA) by arresting the cell cycle and reducing the sensitivity of the epithelium to many cell cycle-active antitumor agents. Potent small-molecule inhibitors of CDK2 were developed using structure-based methods. Topical application of these compounds in a neonatal rat model of CIA reduced hair loss at the site of application in 33 to 50% of the animals. Thus, inhibition of CDK2 represents a potentially useful approach for the prevention of CIA in cancer patients.