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Cordycepin, chemically known as 3'-deoxyadenosine, is a natural nucleoside analogue and bioactive metabolite primarily isolated from fungi of the genus Cordyceps, such as Cordyceps militaris [1, 3]. It is not a therapeutic protein target itself but acts as a small molecule ligand that interferes with various cellular processes by mimicking adenosine [1, 2]. Its primary mechanism of action involves the inhibition of mRNA polyadenylation; lacking a 3'-hydroxyl group, cordycepin is phosphorylated into cordycepin triphosphate and incorporated into growing RNA chains, leading to premature chain termination [1, 6]. Additionally, cordycepin serves as an activator of AMP-activated protein kinase (AMPK), which in turn suppresses the PI3K/Akt/mTOR signaling axis to inhibit cell growth and induce apoptosis in cancerous tissues [6, 16]. These multifaceted interactions contribute to its well-documented anticancer, anti-inflammatory, and immunomodulatory properties [4, 8, 14]. Despite its therapeutic potential, its clinical utility is limited by rapid degradation by adenosine deaminase (ADA) in the bloodstream, often necessitating the use of ADA inhibitors like pentostatin to maintain effective concentrations [3, 11, 13]. Researchers continue to explore its role in treating malignancies and metabolic disorders, focusing on its ability to modulate adaptive stress signaling and cellular homeostasis [2, 17].
Inhibition of mRNA polyadenylation through incorporation into RNA chains as a 3'-deoxyadenosine triphosphate (COR-TP) causing chain termination; activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the PI3K/Akt/mTOR signaling pathways.
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