AOD-9604 vs SLU-PP-332

AOD-9604

AOD-9604 is a synthetic peptide based on the C-terminal segment of human growth hormone, with a tyrosine at its N-terminus and a disulfide bond. It was designed to test the idea that this short region carries some of growth hormone's activity on fat metabolism separately from the rest of the molecule. Work on it began with rodent studies of fat cells and whole-animal lipid metabolism, and the peptide later entered human clinical trials, whose published record is sparse. A smaller body of animal work has looked at cartilage in joint injury models. Unlike full-length growth hormone, it is not regarded as a growth hormone receptor agonist, which shapes how its reported activity is interpreted.

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 AOD-9604 acts

AOD-9604 has been reported not to bind the growth hormone receptor with meaningful affinity and not to act through the IGF-1 axis, so its proposed actions differ from those of the whole hormone. Studies in isolated rodent fat cells and in obese mice examined lipolysis and lipogenesis, and some of that work implicated beta-3 adrenergic receptor pathways. A receptor that binds the fragment directly has not been identified. The cartilage studies used animal joint injury models and measured markers of cartilage matrix, and no mechanism for those observations has been established. Overall, the mechanistic literature is small and comes from a limited number of groups.

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: AOD-9604, Modified hGH fragment (176-191); SLU-PP-332, Small molecule
• Length: AOD-9604, 16 amino acids; SLU-PP-332, not recorded
• Molecular weight: AOD-9604, 1815.1 g/mol; SLU-PP-332, 290.3 g/mol
• Molecular formula: AOD-9604, C78H123N23O23S2; 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.