Aicar vs SLU-PP-332

Aicar

AICAR, also called acadesine, is 5-aminoimidazole-4-carboxamide riboside: a synthetic nucleoside, not a peptide or an amino-acid derivative. Its monophosphate, ZMP, is a natural intermediate in the pathway cells use to build purine nucleotides. AICAR became a standard laboratory tool because cells convert it to ZMP, which mimics AMP and switches on AMP-activated protein kinase (AMPK). A large body of cell and rodent work has used it to study energy sensing, glucose uptake and fatty-acid metabolism. Human clinical work has been limited and has not centred on metabolism. A known weakness of the tool is that ZMP acts on other AMP-sensitive enzymes too, so not every effect attributed to AICAR runs through AMPK.

SLU-PP-332

SLU-PP-332 is a synthetic small molecule, not a peptide, reported to activate all three oestrogen-related receptors: ERRα, ERRβ and ERRγ. Despite their name, these receptors are not activated by oestrogen; they are orphan nuclear receptors, related in structure to the oestrogen receptors but with no confirmed natural ligand. The original reports describe the compound as most active at ERRα. Published work is recent and preclinical, made up of cell studies, including cultured muscle cells, and mouse experiments on skeletal muscle and whole-body energy metabolism. We are not aware of any published human study, and published toxicology data are scarce.

How Aicar acts

AICAR enters cells through adenosine transporters and is phosphorylated by adenosine kinase to ZMP. ZMP binds the regulatory gamma subunit of AMPK at sites that normally sense AMP, and this allosteric activation, together with increased phosphorylation of the catalytic alpha subunit, raises the kinase's activity. Activated AMPK phosphorylates targets such as acetyl-CoA carboxylase, shifting cells away from lipid synthesis and toward processes that generate ATP. ZMP accumulates to high concentrations, however, and has been reported to affect other AMP-regulated enzymes, including fructose-1,6-bisphosphatase and glycogen phosphorylase. Studies that need to separate AMPK-dependent effects often pair AICAR with genetic knockout models.

How SLU-PP-332 acts

ERRs are transcription factors that bind DNA at ERR response elements and act with coactivators, notably PGC-1α, on genes for oxidative phosphorylation, fatty-acid oxidation and the formation of new mitochondria. SLU-PP-332 has been reported to increase ERR-driven transcription in cell-based reporter assays. In mouse skeletal muscle, studies describe higher expression of ERR target genes linked to oxidative metabolism, with some changes reported to depend at least partly on ERRα. Most of this work comes from a small number of laboratories, and independent confirmation is limited.

The records side by side

• Type: Aicar, Nucleoside analogue; SLU-PP-332, Small molecule
• Molecular weight: Aicar, 258.23 g/mol; SLU-PP-332, 290.3 g/mol
• Molecular formula: Aicar, C9H14N4O5; SLU-PP-332, C18H14N2O2

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.