176-191

AOD-9604 (hGH Fragment 176-191)

A 16-amino-acid fragment of human growth hormone engineered to trigger fat metabolism without activating the GH receptor, AOD-9604 cleared early clinical trials for obesity before its pivotal Phase IIb collapsed under a placebo response. Now stripped of FDA Category 2 status and banned by WADA, its most interesting data may be in a direction nobody expected: cartilage repair.

AOD-9604 is a synthetic peptide fragment corresponding to amino acids 176-191 of human growth hormone, with an added N-terminal tyrosine. It selectively activates beta-3 adrenergic receptors to stimulate lipolysis without engaging the GH receptor, producing no measurable effect on IGF-1 or glucose. Its Phase IIb obesity trial (OPTIONS, 536 participants) was terminated in 2007 when placebo outperformed expectations. Preclinical cartilage regeneration data has since repositioned the compound toward joint repair, but no human joint trial exists.