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SMALL MOLECULES THAT BIND CYCLIN-DEPENDENT KINASE INHIBITOR 1B (P27KIP1)

机译:绑定周期依赖性激酶抑制剂1B(P27KIP1)的小分子

摘要

Various compounds and pharmaceutically acceptable salts thereof are provided capable of binding cyclin-dependent kinase inhibitor 1B. The compounds can have a structure according to Formula I or Formula II as detailed herein. The compounds can include SJ747, SJ749, SJ755, SJ757. Pharmaceutical formulations containing the compounds or pharmaceutically acceptable salts are also provided along with methods of use thereof. The formulations and methods can be useful for treating cancer. In some aspects, the cancer is associated with a mislocalization of the intrinsically disordered protein p27. In some aspects, the cancer is resistant to an anticancer therapy. The pharmaceutical formulation can therefore include a second active agent and/or can be given in combination with a second active agent such as a cancer therapeutic. In various aspects, methods of promoting reentry into the cell division cycle in a subject in need thereof using compounds and formulations described herein are also provided.
机译:提供了能够结合细胞周期蛋白依赖性激酶抑制剂1B的各种化合物及其药学上可接受的盐。所述化合物可具有如本文详述的根据式I或式II的结构。这些化合物可以包括SJ747,SJ749,SJ755,SJ757。还提供了包含化合物或药学上可接受的盐的药物制剂及其使用方法。所述制剂和方法可用于治疗癌症。在某些方面,该癌症与固有失调的蛋白质p27的错位有关。在某些方面,癌症对抗癌疗法有抗性。因此,药物制剂可以包含第二活性剂和/或可以与第二活性剂例如癌症治疗剂组合给予。在各个方面,还提供了使用本文所述的化合物和制剂在需要其的受试者中促进重入细胞分裂循环的方法。

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