EPAC靶向治疗的未来：激动剂与拮抗剂
药物对cAMP水平的作用，主要通过激活cAMP(EPAC)和蛋白激酶A(PKA)信号通路进行的。 2015年3月在《Trends in pharmacological sciences》(药理学趋势)杂志发表的文章指出，近期以cAMP为基础的治疗方向已经开始转向EPAC亚型的特异性调控(EPAC1和EPAC2)，其能够作为一种更有针对性的治疗方法。例如，EPAC2选择性激动剂可以从促进胰腺β细胞的胰岛素分泌，EPAC1选择性激动剂在血管炎症治疗方面是有用效果的。同时，EPAC1和EPAC2拮抗剂都可用于
药物对cAMP水平的作用，主要通过激活cAMP(EPAC)和蛋白激酶A(PKA)信号通路进行的。
2015年3月在《Trends in pharmacological sciences》(药理学趋势)杂志发表的文章指出，近期以cAMP为基础的治疗方向已经开始转向EPAC亚型的特异性调控(EPAC1和EPAC2)，其能够作为一种更有针对性的治疗方法。例如，EPAC2选择性激动剂可以从促进胰腺β细胞的胰岛素分泌，EPAC1选择性激动剂在血管炎症治疗方面是有用效果的。同时，EPAC1和EPAC2拮抗剂都可用于治疗心脏衰竭。该文章提出了设计EPAC选择性激动剂或拮抗剂的方法，目前的策略主要是开发具有异构体选择性的、对EPAC1和EPAC2有活性的小分子调节剂。
The future of EPAC-targeted therapies: agonism versus antagonism.
Parnell E1, Palmer TM2, Yarwood SJ3.
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Abstract
Pharmaceutical manipulation of cAMP levels exerts beneficial effects through the regulation of the exchange protein activated by cAMP (EPAC) and protein kinase A (PKA) signalling routes. Recent attention has turned to the specific regulation of EPAC isoforms (EPAC1 and EPAC2) as a more targeted approach to cAMP-based therapies. For example, EPAC2-selective agonists could promote insulin secretion from pancreatic β cells, whereas EPAC1-selective agonists may be useful in the treatment of vascular inflammation. By contrast, EPAC1 and EPAC2 antagonists could both be useful in the treatment of heart failure. Here we discuss whether the best way forward is to design EPAC-selective agonists or antagonists and the current strategies being used to develop isoform-selective, small-molecule regulators of EPAC1 and EPAC2 activity.
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