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AICAR (Acadesine)

F
lead outcome
Endurance / exercise performance (the…
grades vary by outcome ↓
Small molecule (non-peptide)⚠ WADA-banned
also called — AICAR · AICAr · Acadesine (its drug name) · AICA-riboside · 5-aminoimidazole-4-carboxamide ribonucleoside · (intracellular active form: ZMP). INCI: none
metabolicendurance / performance (exercise mimetic)fat oxidationinsulin sensitivity(cardioprotection, as Acadesine)

The original "exercise in a pill" — and the register's best doping-scandal story. This entry closes the exercise-mimetic triad and carries genuine intrigue. Three threads: (1) it's the compound behind the famous "44% more endurance in sedentary mice" headline that coined "exercise mimetic"; (2) that finding triggered a real Tour de France doping saga — arrests, a supply network, and the twist that the scientist who discovered its performance effect also built the test to catch it; (3) it lived a double life — a legitimate cardiac-surgery drug candidate (Acadesine) and the lab's #1 AMPK tool — until a 2021 review revealed many of its effects aren't even AMPK-dependent. Zero human endurance data; it's a small molecule, not a peptide.

In brief

AICAR (Acadesine) is a small-molecule AMPK activator — not a peptide — and the original "exercise in a pill." By entering cells and mimicking AMP (as ZMP), it switches on AMPK, the master energy sensor, triggering a metabolic shift toward fat oxidation, insulin-independent glucose uptake, mitochondrial biogenesis (PGC-1α) and autophagy. Its fame comes from Narkar et al. (Cell, 2008): sedentary mice given AICAR for 4 weeks ran ~44% longer with no training — the study that coined "exercise mimetic." That headline launched a genuine doping saga: WADA banned it in 2009, French authorities suspected it at the Tour de France, and a supply-network bust followed in 2012 — with the striking irony that the discoverer of its performance effect (Ronald Evans) also created the anti-doping test for it. Meanwhile it lived a double life as a legitimate cardiac-surgery drug candidate and the lab's #1 AMPK research tool — until a 2021 review showed many of its effects are AMPK-independent, complicating decades of interpretation. The honest bottom line: elegant, historically important biology; zero human endurance data; a banned, detectable substance in sport; and a mechanism messier than its "clean AMPK activator" reputation.

Legal standing, by region
European Union
Not FDA-approved (gray-market)

not an approved consumer drug; Acadesine did not reach general approval. Investigational / research chemical. Not a cosmetic.

⚠ WADA-prohibited in sportSport — WADA-prohibited since 2009 (S4 metabolic modulators), banned at all times, in and out of competition; detectable in blood/urine; serious sanctions. This is one of the register's most enforcement-relevant compounds in a sporting context.
Evidence, by outcome
How we grade →

An honest grade per outcome — drawn from the evidence, not any catalogue. Hype and undemonstrated marketing claims grade low.

OutcomeEvidence base · effectGrade
Endurance / exercise performance (the marketed use)
Landmark — but mouse-only; no human endurance trials; WADA-banned precisely for this
Narkar 2008 (Cell): sedentary mice +~44% running endurance, type-I fiber shift
F
Fat oxidation / metabolic / insulin sensitivity
Strong mechanistic/animal data; not established as a human therapeutic
Well-characterised: AMPK → ACC inactivation, GLUT4, PGC-1α (cells + animals)
F
Cardioprotection (Acadesine, cardiac surgery)
Real clinical study history — but did not achieve general approval; not a consumer indication
Legitimate clinical trials in cardiac-surgery ischemia
C
AMPK-activation (as a research tool)
BUT 2021 review: many effects AMPK-independent → interpret AICAR-only studies cautiously
Decades of use as the standard AMPK probe
B
Human safety (self-use)
Trials: transient uric-acid rise, mild lactic acidosis, possible hypoglycemia (insulin-independent glucose uptake); no organ-toxicity signal noted — but gray-market self-injection is unstudied, and it's banned/detectable in sport
Trial data at therapeutic doses
Disclosure

Vallydia sells its own cosmetic serums, and some ingredients graded here belong to the same categories as those products. Grades are drawn from the published evidence by the method we publish, and applied to our own ingredients on the same terms — our copper-peptide serum is graded no more kindly than the peptides it competes with. We disclose the interest so you can weigh it.

Trade names shown here (for example Matrixyl, Argireline, Syn-Ake) are the property of their respective owners and are used only to identify the ingredient under discussion. Their appearance implies no affiliation with, or endorsement by, the proprietor.

Evidence changes

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Identity

a cell-permeable small molecule — a purine nucleoside — that acts as a pharmacological activator of AMPK (AMP-activated protein kinase), the cell's "master metabolic energy sensor." It is itself biologically inert until it enters cells (via adenosine transporters) and is phosphorylated to ZMP, an AMP-mimic that allosterically switches AMPK on. It has been the most widely used AMPK activator in laboratory research for decades — and, separately, a clinical drug candidate (Acadesine).

Mechanism (as proposed)

AICAR is a nucleoside that enters cells through adenosine transporters (ENT1/2, CNT2/3), where it's phosphorylated to ZMP — a molecule that mimics AMP. Rising "AMP-like" signal allosterically activates AMPK, the master sensor that cells use to detect low energy. Activated AMPK flips the metabolic switch from anabolic (storing) to catabolic (burning): it phosphorylates/inactivates ACC (↑fatty-acid oxidation), translocates GLUT4 (↑glucose uptake, insulin-independent), activates PGC-1α (↑mitochondrial biogenesis), and inhibits mTORC1 (↓protein synthesis, ↑autophagy) — collectively reproducing much of the muscle's response to endurance exercise. Elegant and foundational — but note the 2021 caveat that some AICAR actions bypass AMPK entirely.

Chemical identifiers

Cross-reference identifiers for the authoritative external databases — not a recipe, and nothing about how to use it.

PubChem CID65110
InChIKeyNOTGFIUVDGNKRI-UUOKFMHZSA-N
SMILESC1=NC(=C(N1[C@H]2[C@@H]([C@@H]([C@H](O2)COP(=O)(O)O)O)O)N)C(=O)N
UNIIF0X88YW0YK
DrugBankDB01700

via PubChem exact-name match (AICAR) · high confidence

Sources — 5 cited
01Narkar VA, et al. AMPK and PPARδ Agonists Are Exercise Mimetics. Cell. 2008;134:405-415 (the ~44% endurance / "exercise mimetic" paper; Evans lab, Salk).
02Visnjic D, et al. AICAr, a widely used AMPK activator with important AMPK-independent effects: a systematic review. Cells. 2021 (the AMPK-independence caveat).
03WADA Prohibited List (AICAR added 2009; S4 metabolic modulators); doping-control detection methodology for AICAR/GW501516 (Evans-derived methods).
04Acadesine cardiac-surgery clinical literature (myocardial protection/ischemia); Corton JM, et al. Eur J Biochem. 1995 (AICAR as AMPK activator).
05(No human endurance-efficacy trials; partner compound GW501516 dropped for carcinogenicity.)
Updated 2026-07-13 (status: foundational animal data, no human endurance trials, WADA-banned; watch AMPK-activator drug development — e.g. next-gen activators like O304 — rather than AICAR itself)

Grades reflect the published evidence, not our interest. No dosing, reconstitution, or administration is published for research compounds — that restraint is deliberate.

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