AOD-9604 vs SLU-PP-332

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.

SLU-PP-332 activates all three ERR isoforms (α, β, γ) with a modest potency preference for ERRα — orphan nuclear receptors that regulate oxidative metabolism gene programs. Activation drives PGC-1α co-activator pathways, mitochondrial biogenesis (TFAM, NRF1), fatty acid oxidation (CPT1B, ACADM), and a shift toward oxidative type IIa muscle fibers. Note: despite the ERR name, these receptors do not bind estrogen.

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