AICAR

A purine nucleoside analogue studied as a pharmacological AMPK-pathway probe in cell biology and preclinical metabolic research models.

Molecular Profile

Type
Purine nucleoside analogue (imidazole ribonucleoside)
Molecular formula
C9H14N4O5
Molecular weight
258.23 g/mol
CAS number
2627-69-2

Mechanism & Target Class

AICAR enters cells through equilibrative nucleoside transporters and is phosphorylated by adenosine kinase to its 5′-monophosphate form, ZMP (AICAR monophosphate; CAS 3031-94-5). ZMP is a structural AMP analogue that occupies nucleotide-binding sites on the regulatory γ-subunit of AMP-activated protein kinase (AMPK), the heterotrimeric αβγ serine/threonine kinase. Binding allosterically activates AMPK and protects the activation-loop residue Thr172 from dephosphorylation. Downstream, active AMPK phosphorylates acetyl-CoA carboxylase (ACC), inhibits mTORC1 signaling, promotes GLUT4-mediated glucose transporter translocation, and activates PGC-1α-driven transcriptional programs involved in mitochondrial biogenesis. Because ZMP also interacts with other AMP-regulated enzymes — including fructose-1,6-bisphosphatase — and some cellular responses to AICAR proceed through AMPK-independent pathways, researchers pair AICAR with dominant-negative AMPK constructs and adenosine-kinase inhibitors as orthogonal controls to establish pathway specificity.

Storage & Handling

Lyophilized
Store crystalline powder at −20°C, desiccated and protected from moisture; ship cold.
Handling
Water-soluble; protect from light and moisture; keep sealed; standard laboratory reagent precautions apply.

Primary Database

PubChem CID 65110 ↗

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