Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China.
Department of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042, China.
Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129759. doi: 10.1016/j.bbagen.2020.129759. Epub 2020 Oct 8.
Protein kinases play a fundamental role in the intracellular transduction because of their ability to phosphorylate plethora of proteins. Over the past three decades, numerous protein kinase inhibitors have been identified and are being used clinically successfully. The biodiversity of marine organisms provides a rich source for the discovery and development of novel anticancer agents in the treatment of human malignancies and a lot of bioactive ingredients from marine organisms display anticancer effects by affecting the protein kinases-mediated pathways. In the present mini-review, anticancer compounds from marine source were reviewed and discussed in context of their targeted pathways associated with protein kinases and the progress of these compounds as anticancer agents in recent five years were emphasized. The molecular entities and their modes of actions were presented. We focused on protein kinases-mediated signaling pathways including PI3K/Akt/mTOR, p38 MAPK, and EGFR. The marine compounds targeting special pathways of protein kinases were highlighted. We have also discussed the existing challenges and prospects related to design and development of novel protein kinase inhibitors from marine sources.
蛋白激酶在细胞内转导中起着至关重要的作用,因为它们能够磷酸化大量的蛋白质。在过去的三十年中,已经鉴定出许多蛋白激酶抑制剂,并成功地应用于临床。海洋生物的多样性为发现和开发新型抗癌药物提供了丰富的资源,用于治疗人类恶性肿瘤,许多来自海洋生物的生物活性成分通过影响蛋白激酶介导的途径显示出抗癌作用。在本综述中,讨论了海洋来源的抗癌化合物,根据它们与蛋白激酶相关的靶向途径进行了综述,并强调了这些化合物在最近五年作为抗癌药物的进展。介绍了分子实体及其作用模式。我们重点关注蛋白激酶介导的信号通路,包括 PI3K/Akt/mTOR、p38 MAPK 和 EGFR。针对蛋白激酶特殊途径的海洋化合物被突出显示。我们还讨论了与设计和开发新型蛋白激酶抑制剂相关的现有挑战和前景。