Department of Medical Chemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72 Av., 70-111 Szczecin, Poland.
Department of Biochemistry, Pomeranian Medical University in Szczecin, Powstancow Wlkp. 72 Av., 70-111 Szczecin, Poland.
Int J Mol Sci. 2021 Mar 10;22(6):2806. doi: 10.3390/ijms22062806.
Recent studies on cyclin-dependent kinase (CDK) inhibitors have revealed that small molecule drugs have become very attractive for the treatment of cancer and neurodegenerative disorders. Most CDK inhibitors have been developed to target the ATP binding pocket. However, CDK kinases possess a very similar catalytic domain and three-dimensional structure. These features make it difficult to achieve required selectivity. Therefore, inhibitors which bind outside the ATP binding site present a great interest in the biomedical field, both from the fundamental point of view and for the wide range of their potential applications. This review tries to explain whether the ATP competitive inhibitors are still an option for future research, and highlights alternative approaches to discover more selective and potent small molecule inhibitors.
最近关于细胞周期蛋白依赖性激酶（CDK）抑制剂的研究表明，小分子药物已成为治疗癌症和神经退行性疾病的非常有吸引力的选择。大多数 CDK 抑制剂的开发都是针对 ATP 结合口袋的。然而，CDK 激酶具有非常相似的催化结构域和三维结构。这些特征使得难以实现所需的选择性。因此，与 ATP 结合位点结合的抑制剂在生物医学领域都引起了极大的关注，无论是从基础的角度来看，还是从它们广泛的潜在应用来看都是如此。本文综述试图解释 ATP 竞争抑制剂是否仍然是未来研究的一个选择，并强调了发现更具选择性和更有效的小分子抑制剂的替代方法。
