Cordycepin

Cordycepin at a Glance

Cordycepin (3’-deoxyadenosine) is the signature nucleoside of Cordyceps militaris — an adenosine analogue missing a single hydroxyl group, which is enough to make it terminate RNA chains when incorporated.

That mechanism drives most of cordyceps’ preclinical anticancer and anti-inflammatory claims.

Its problem is the same missing group. Cordycepin is rapidly destroyed by adenosine deaminase in blood, which is why serious attempts to develop it pair it with a deaminase inhibitor — and why oral cordyceps products are unlikely to deliver meaningful systemic cordycepin.

What It's Used For

Cordycepin (3’-deoxyadenosine) is the signature nucleoside of Cordyceps militaris and the molecule behind most of cordyceps’ preclinical anticancer and anti-inflammatory reputation. Structurally it is adenosine missing its 3’-hydroxyl, and that single change defines both its mechanism and its problem. The mechanism: lacking a 3’-OH, it is incorporated into RNA as a chain terminator and blocks polyadenylation, disrupting RNA synthesis ^{4,12Reference 4Wei C et al. · 2019Cordycepin inhibits drug-resistant non-small-cell lung cancer progression by activating the AMPK signalling pathwayView study →Reference 12Tuli HS et al. · 2013Cordycepin: a bioactive metabolite with therapeutic potentialView study →}.

The problem: being a near-perfect adenosine mimic, it is rapidly deaminated by adenosine deaminase (ADA) to the largely inactive 3’-deoxyinosine, giving a minutes-scale half-life and poor oral bioavailability ^{9Reference 9Qi C et al. · 2023AnimalSimultaneous determination of cordycepin and its metabolite 3’-deoxyinosine in rat whole blood by UHPLC-Q Exactive HRMS and application to pharmacokinetic studyView study →}.

That liability has pushed drug development away from the molecule itself and toward a ProTide prodrug, NUC-7738, which is the source of the only human clinical data here ^{11Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}.

Note up front: the “energy/stamina/libido” reputation belongs to whole cordyceps tradition, not to any isolated-cordycepin study.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Isolated cordycepin is preclinical, so scores stay low by design. Each application links to its write-up.

01AnticancerShaky44%In-vitro + rodent, plus a first-in-human trial of a prodrug ^{4,5,11Reference 4Wei C et al. · 2019Cordycepin inhibits drug-resistant non-small-cell lung cancer progression by activating the AMPK signalling pathwayView study →Reference 5Hwang JH et al. · 2017Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric-oxide-mediated ERK/Slug signallingView study →Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}

02Anti-inflammatoryShaky36%Multiple rodent + macrophage models ^{1,2,3Reference 1Kim HG et al. · 2006Cordycepin inhibits lipopolysaccharide-induced inflammation by suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cellsView study →Reference 2Zhang Y et al. · 2022AnimalCordycepin induces M1/M2 macrophage polarization to attenuate liver and lung damage in immature septic mice via NF-κB/p65 inhibitionView study →Reference 3Ashraf S et al. · 2019AnimalThe polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritisView study →}

03Metabolic / lipid-loweringShaky24%Single-species rodent models ^{6,7Reference 6Ma L et al. · 2015AnimalCordycepin from Cordyceps militaris prevents hyperglycemia in alloxan-induced diabetic miceView study →Reference 7Gao J et al. · 2011AnimalLipid-lowering effect of cordycepin (3’-deoxyadenosine) from Cordyceps militaris on hyperlipidaemic hamsters and ratsView study →}

04AntiviralShaky18%Dated in-vitro, RNA chain-termination rationale ^{12Reference 12Tuli HS et al. · 2013Cordycepin: a bioactive metabolite with therapeutic potentialView study →}

Mechanisms

Pharmacokinetics

The defining problem. Because cordycepin is a near-perfect adenosine mimic, it is rapidly deaminated by adenosine deaminase (ADA) to the largely inactive 3’-deoxyinosine, giving a very short plasma half-life — rat whole-blood work confirms cordycepin is consumed rapidly with 3’-deoxyinosine as the dominant circulating metabolite ^{9Reference 9Qi C et al. · 2023AnimalSimultaneous determination of cordycepin and its metabolite 3’-deoxyinosine in rat whole blood by UHPLC-Q Exactive HRMS and application to pharmacokinetic studyView study →}. Oral bioavailability of intact cordycepin is poor-to-negligible; one study argues the apparent oral effect may run through a “nucleoside rescue” route, where absorbed 3’-deoxyinosine is re-converted intracellularly to cordycepin triphosphate rather than intact cordycepin surviving first pass ^{10Reference 10Lee JB et al. · 2019A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepinView study →}. Two workarounds define the field: co-administration with an ADA inhibitor (pentostatin) to keep cordycepin intact ^{12Reference 12Tuli HS et al. · 2013Cordycepin: a bioactive metabolite with therapeutic potentialView study →}, and the modern NUC-7738 ProTide prodrug, which bypasses ADA deamination and the rate-limiting first phosphorylation to deliver the active triphosphate intracellularly at far higher potency ^{11Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}. The bottom line: intact-cordycepin systemic exposure from oral supplementation is low and fleeting, so efficacy figures from injected or ADA-protected preclinical work do not transfer to oral fruiting-body dosing.

Clinical trials

For isolated cordycepin there are no completed human efficacy trials. Human clinical data exist only for the prodrug NUC-7738, tested in the first-in-human NuTide:701 Phase I study in advanced solid tumors — reported well-tolerated with early signs of anticancer activity ^{11Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}. This is a chemically distinct ProTide (much more potent than cordycepin in vitro), engineered specifically to overcome cordycepin’s ADA/pharmacokinetic liabilities, so it is evidence for the scaffold, not for taking cordycepin. Whole-herb cordyceps human trials exist but are not cordycepin-specific and belong to the herb page.

Last checked: July 2026.

Toxicity & Safety

Cordycepin is an antiproliferative/cytotoxic nucleoside analogue — the same RNA-directed activity that makes it an anticancer candidate is intrinsically a genotoxic, antiproliferative liability rather than a benign “tonic” profile ^{4,12Reference 4Wei C et al. · 2019Cordycepin inhibits drug-resistant non-small-cell lung cancer progression by activating the AMPK signalling pathwayView study →Reference 12Tuli HS et al. · 2013Cordycepin: a bioactive metabolite with therapeutic potentialView study →}, which is why it is flagged moderate and should not inherit the low-risk framing of whole-herb cordyceps. Preclinical data are generally well-tolerated at studied doses, but no formal human safety dossier exists for the isolated molecule (the human tolerability data are for NUC-7738, a different entity) ^{11Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}. The interaction surface follows from its adenosine mimicry: ADA inhibitors (pentostatin) and other agents that raise ADA-substrate levels will markedly increase cordycepin exposure and potentiate cytotoxicity; adenosine and adenosine-receptor drugs (dipyridamole, adenosine itself, methylxanthines as receptor antagonists) are plausible pharmacodynamic interactions; and additive risk with cytotoxic chemotherapy is theoretical but expected ^{12Reference 12Tuli HS et al. · 2013Cordycepin: a bioactive metabolite with therapeutic potentialView study →}.

Dosage

There is no established or validated human oral dose for isolated cordycepin, and nothing here is a recommendation. Preclinical rodent studies typically use ~10–60 mg/kg (oral or intraperitoneal), often with ADA protection, which is not human-translatable. Supplements sell Cordyceps militaris extracts standardized to a stated cordycepin content, but purified cordycepin has no clinical dosing standard and its poor oral stability makes any oral figure unreliable. NUC-7738 (the prodrug, given intravenously on a trial-defined escalation) is a separate agent — its dosing is not a cordycepin dose ^{11Reference 11Schwenzer H et al. · 2021Clinical trialThe novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trialView study →}.

References

1. Kim HG, et al. (2006). Cordycepin inhibits lipopolysaccharide-induced inflammation by suppression of NF-κB through Akt and p38 inhibition in RAW 264.7 macrophage cells. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/16899239/
2. Zhang Y, Cheng J, Su Y, et al. (2022). Cordycepin induces M1/M2 macrophage polarization to attenuate liver and lung damage in immature septic mice via NF-κB/p65 inhibition. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/34850068/
3. Ashraf S, et al. (2019). The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/30886197/
4. Wei C, et al. (2019). Cordycepin inhibits drug-resistant non-small-cell lung cancer progression by activating the AMPK signalling pathway. Pharmacological Research. https://pubmed.ncbi.nlm.nih.gov/30974169/
5. Hwang JH, et al. (2017). Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric-oxide-mediated ERK/Slug signalling. American Journal of Cancer Research. https://pubmed.ncbi.nlm.nih.gov/28401001/
6. Ma L, et al. (2015). Cordycepin from Cordyceps militaris prevents hyperglycemia in alloxan-induced diabetic mice. Nutrition Research. https://pubmed.ncbi.nlm.nih.gov/25940982/
7. Gao J, et al. (2011). Lipid-lowering effect of cordycepin (3’-deoxyadenosine) from Cordyceps militaris on hyperlipidaemic hamsters and rats. Yao Xue Xue Bao (Acta Pharmaceutica Sinica). https://pubmed.ncbi.nlm.nih.gov/21882527/
8. Yang X, et al. (2015). Cordycepin alleviates airway hyperreactivity in a murine model of asthma by attenuating the inflammatory process. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/25912153/
9. Qi C, et al. (2023). Simultaneous determination of cordycepin and its metabolite 3’-deoxyinosine in rat whole blood by UHPLC-Q Exactive HRMS and application to pharmacokinetic study. Journal of Separation Science. https://pubmed.ncbi.nlm.nih.gov/36377517/
10. Lee JB, Radhi M, Cipolla E, et al. (2019). A novel nucleoside rescue metabolic pathway may be responsible for the therapeutic effect of orally administered cordycepin. Scientific Reports. https://pubmed.ncbi.nlm.nih.gov/31673018/
11. Schwenzer H, et al. (2021). The novel nucleoside-analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase I clinical trial. Clinical Cancer Research. https://pubmed.ncbi.nlm.nih.gov/34497073/
12. Tuli HS, et al. (2013). Cordycepin: a bioactive metabolite with therapeutic potential. Life Sciences. https://pubmed.ncbi.nlm.nih.gov/24121015/

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