AOD-9604 vs SLU-PP-915

Metabolic

Metabolic

Research Only

Research Only

The original preclinical hypothesis was that hGH(177-191) retains a lipolytic activity via a non-GH-receptor pathway, with some rodent data implicating β3-adrenoceptor expression and cAMP signaling in adipocytes. This mechanism is disputed and has not been robustly reproduced in controlled human studies — Phase 2 trials showed no significant effect on body weight versus placebo. AOD-9604 does not measurably raise serum IGF-1 and does not impair glucose tolerance in human safety studies, which is consistent with lack of GH-receptor agonism but does not establish clinical lipolytic efficacy.

The estrogen-related receptors (ERRα/β/γ) are orphan nuclear receptors that act as master transcriptional regulators of oxidative metabolism, driving mitochondrial biogenesis, oxidative phosphorylation, fatty-acid oxidation, and the TCA cycle — largely as partners of the PGC-1 coactivators. SLU-PP-915 binds and activates all three ERR isoforms with an EC50 of roughly 400 nM at each. In its medicinal-chemistry design, the phenol and aniline groups of earlier ERR agonists were replaced with a boronic-acid moiety on a disubstituted thiophene scaffold, which preserved receptor activity while improving microsomal metabolic stability and oral exposure. In cells and in rodents it upregulates canonical ERR target genes including PGC-1α, lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 4 (PDK4), and DNA-damage-inducible transcript 4 (DDIT4).

Short; reported plasma half-life on the order of minutes in preclinical work. Well-characterized human PK data are limited.

Not established in humans; engineered for improved metabolic stability and oral exposure relative to first-generation ERR agonists