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Epac as a tractable therapeutic target

Slika, Hasan; Mansour, Hadi; Nasser, Suzanne; Shaito, Abdullah; Kobeissy, Firas; N. Orekhov, Alexander; Pintus, Gianfranco; Eid, Ali

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Hasan Slika

Hadi Mansour

Abdullah Shaito

Firas Kobeissy

Alexander N. Orekhov

Gianfranco Pintus

Ali Eid


In 1957, cyclic adenosine monophosphate (cAMP) was identified as the first secondary messenger, and the first signaling cascade discovered was the cAMP-protein kinase A (PKA) pathway. Since then, cAMP has received increasing attention given its multitude of actions. Not long ago, a new cAMP effector named exchange protein directly activated by cAMP (Epac) emerged as a critical mediator of cAMP's actions. Epac mediates a plethora of pathophysiologic processes and contributes to the pathogenesis of several diseases such as cancer, cardiovascular disease, diabetes, lung fibrosis, neurological disorders, and others. These findings strongly underscore the potential of Epac as a tractable therapeutic target. In this context, Epac modulators seem to possess unique characteristics and advantages and hold the promise of providing more efficacious treatments for a wide array of diseases. This paper provides an in-depth dissection and analysis of Epac structure, distribution, subcellular compartmentalization, and signaling mechanisms. We elaborate on how these characteristics can be utilized to design specific, efficient, and safe Epac agonists and antagonists that can be incorporated into future pharmacotherapeutics. In addition, we provide a detailed portfolio for specific Epac modulators highlighting their discovery, advantages, potential concerns, and utilization in the context of clinical disease entities.


Slika, H., Mansour, H., Nasser, S., Shaito, A., Kobeissy, F., N. Orekhov, A., …Eid, A. (2023). Epac as a tractable therapeutic target. European Journal of Pharmacology, 945, Article 175645.

Journal Article Type Article
Acceptance Date Mar 6, 2023
Publication Date 2023-04
Publicly Available Date May 30, 2023
Journal European Journal of Pharmacology
Print ISSN 0014-2999
Electronic ISSN 1879-0712
Publisher Elsevier
Volume 945
Article Number 175645
Keywords cAMP, Epac; Cancer; Cardiovascular disease; Pharmacotherapeutics
Publisher URL


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