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Pim kinase inhibitors in cancer: medicinal chemistry insights into their activity and selectivity
Drug Discovery Today ( IF 7.4 ) Pub Date : 2020-09-21 , DOI: 10.1016/j.drudis.2020.09.017
Soraya Alnabulsi , Enas A. Al-Hurani

The oncogenic Pim kinase proteins (Pim-1/2/3) regulate tumorigenesis through phosphorylating essential proteins that control cell cycle and proliferation. Pim kinase is a potential chemotherapeutic target in cancer and its inhibition is currently the focus of intensive drug design and development efforts. The distinctive presence of proline amino acids in the hinge region provides an opportunity to inhibit Pim kinase while conserving the physiological functions of other kinases and reducing the toxicity profiles of the inhibitors. Various Pim kinase inhibitors have been clinically evaluated for the treatment of hematological cancers, yet none has reached the clinic. In this review, we discuss the design and development of selective and potent Pim inhibitors with novel chemotypes focusing on structural features essential for high potency and selectivity.



中文翻译:

癌症中的Pim激酶抑制剂:其活性和选择性的药物化学见解

致癌的Pim激酶蛋白(Pim-1 / 2/3)通过磷酸化控制细胞周期和增殖的必需蛋白来调节肿瘤发生。Pim激酶是癌症中潜在的化学治疗靶标,其抑制作用目前是药物设计和开发的重点。脯氨酸氨基酸在铰链区中的独特存在为抑制Pim激酶提供了机会,同时又保留了其他激酶的生理功能并降低了抑制剂的毒性。临床上已评估了各种Pim激酶抑制剂用于治疗血液系统癌症,但尚未进入临床。在这篇评论中

更新日期:2020-11-15
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