Anton Débora Bublitz, Ducati Rodrigo Gay, Timmers Luís Fernando Saraiva Macedo, Laufer Stefan, Goettert Márcia Inês
Biotechnology Graduate Program, Universidade do Vale do Taquari (Univates), Lajeado, Rio Grande do Sul CEP 95914-014, Brazil.
Medical Science Graduate Program, Universidade do Vale do Taquari (Univates), Lajeado, Rio Grande do Sul CEP 95914-014, Brazil.
Cancers (Basel). 2021 Apr 25;13(9):2077. doi: 10.3390/cancers13092077.
The p38δ mitogen-activated protein kinase is an important signal transduction enzyme. p38δ has recently emerged as a drug target due to its tissue-specific expression patterns and its critical roles in regulation of cellular processes related to cancer and inflammatory diseases, such as cell proliferation, cell migration, apoptosis, and inflammatory responses. However, potent and specific p38δ inhibitors have not been defined so far. Moreover, in cancer disease, p38δ appears to act as a tumor suppressor or tumor promoter according to cancer and cell type studied. In this review, we outline the current understanding of p38δ roles in each cancer type, to define whether it is possible to delineate new cancer therapies based on small-molecule p38δ inhibitors. We also highlight recent advances made in the design of molecules with potential to inhibit p38 isoforms and discuss structural approaches to guide the search for p38δ inhibitors.
p38δ丝裂原活化蛋白激酶是一种重要的信号转导酶。由于其组织特异性表达模式及其在调控与癌症和炎症性疾病相关的细胞过程（如细胞增殖、细胞迁移、细胞凋亡和炎症反应）中的关键作用，p38δ最近已成为一种药物靶点。然而，迄今为止尚未确定强效且特异性的p38δ抑制剂。此外，在癌症疾病中，根据所研究的癌症和细胞类型，p38δ似乎可作为肿瘤抑制因子或肿瘤促进因子。在本综述中，我们概述了目前对p38δ在每种癌症类型中作用的理解，以确定是否有可能基于小分子p38δ抑制剂来制定新的癌症治疗方法。我们还强调了在设计具有抑制p38亚型潜力的分子方面取得的最新进展，并讨论了指导寻找p38δ抑制剂的结构方法。
