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磷酸二酯酶7抑制剂的研发进展

Advances in the development of phosphodiesterase 7 inhibitors.

作者信息

Huang Jia-Xi, Zhu Bo-Lin, Xu Jiang-Ping, Zhou Zhong-Zhen

机构信息

Innovation Program of Drug Research on Neurological and Metabolic Diseases, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.

Innovation Program of Drug Research on Neurological and Metabolic Diseases, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China; Pharmacy Department, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China.

出版信息

Eur J Med Chem. 2023 Mar 15;250:115194. doi: 10.1016/j.ejmech.2023.115194. Epub 2023 Feb 9.

Abstract

Phosphodiesterase 7 (PDE7) specifically hydrolyzes cyclic adenosine monophosphate (cAMP), a second messenger that plays essential roles in cell signaling and physiological processes. Many PDE7 inhibitors used to investigate the role of PDE7 have displayed efficacy in the treatment of a wide range of diseases, such as asthma and central nervous system (CNS) disorders. Although PDE7 inhibitors are developed more slowly than PDE4 inhibitors, there is increasing recognition of PDE7 inhibitors as potential therapeutics for no nausea and vomiting secondary. Herein, we summarized the advances in PDE7 inhibitors over the past decade, focusing on their crystal structures, key pharmacophores, subfamily selectivity, and therapeutic potential. Hopefully, this summary will lead to a better understanding of PDE7 inhibitors and provide strategies for developing novel therapies targeting PDE7.

摘要

磷酸二酯酶7(PDE7)特异性水解环磷酸腺苷(cAMP),cAMP是一种在细胞信号传导和生理过程中起关键作用的第二信使。许多用于研究PDE7作用的PDE7抑制剂在治疗多种疾病(如哮喘和中枢神经系统(CNS)疾病)方面已显示出疗效。尽管PDE7抑制剂的研发速度比PDE4抑制剂慢,但人们越来越认识到PDE7抑制剂作为无继发恶心和呕吐的潜在治疗药物。在此,我们总结了过去十年中PDE7抑制剂的研究进展,重点关注其晶体结构、关键药效团、亚家族选择性和治疗潜力。希望这一总结能增进对PDE7抑制剂的理解,并为开发靶向PDE7的新型疗法提供策略。

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