Research Institute of Pharmaceutical Sciences, College of Pharmacy , Seoul National University , Seoul 08826 , Korea.
J Med Chem. 2018 Nov 21;61(22):9791-9810. doi: 10.1021/acs.jmedchem.8b00185. Epub 2018 Jul 20.
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a member of an evolutionarily conserved family of protein kinases that belongs to the CMGC group of kinases. DYRK1A, encoded by a gene located in the human chromosome 21q22.2 region, has attracted attention due to its association with both neuropathological phenotypes and cancer susceptibility in patients with Down syndrome (DS). Inhibition of DYRK1A attenuates cognitive dysfunctions in animal models for both DS and Alzheimer's disease (AD). Furthermore, DYRK1A has been studied as a potential cancer therapeutic target because of its role in the regulation of cell cycle progression by affecting both tumor suppressors and oncogenes. Consequently, selective synthetic inhibitors have been developed to determine the role of DYRK1A in various human diseases. Our perspective includes a comprehensive review of potent and selective DYRK1A inhibitors and their forthcoming therapeutic applications.
双特异性酪氨酸磷酸化调节激酶 1A（DYRK1A）是一种进化上保守的蛋白激酶家族成员，属于 CMGC 激酶组。DYRK1A 由位于人类染色体 21q22.2 区域的基因编码，由于其与唐氏综合征（DS）患者的神经病理表型和癌症易感性有关，因此引起了关注。抑制 DYRK1A 可减轻 DS 和阿尔茨海默病（AD）动物模型中的认知功能障碍。此外，由于 DYRK1A 通过影响肿瘤抑制基因和癌基因来调节细胞周期进程，因此它被研究为一种潜在的癌症治疗靶点。因此，已经开发了选择性合成抑制剂来确定 DYRK1A 在各种人类疾病中的作用。我们的观点包括对有效且选择性的 DYRK1A 抑制剂及其即将到来的治疗应用的全面综述。
