Growth Hormone Axis

AOD-9604 is a 16-amino-acid C-terminal fragment (aa 177-191 + N-terminal Tyr) of human GH that retains lipolytic activity via β3-adrenergic receptor upregulation without growth-promoting, diabetogenic, or IGF-1-stimulating effects. Phase 2b obesity trials failed, but cartilage regeneration research continues.

CJC-1295 with DAC is a synthetic 30-amino acid GHRH analog with a Drug Affinity Complex that enables covalent albumin binding, extending half-life from ~7 minutes (native GHRH) to 5.8-8.1 days. Phase 1/2 trials demonstrated GH increases of 2-10 fold for 6+ days and IGF-1 rises of 1.5-3 fold lasting 9-11 days per dose.

Mod GRF 1-29 is a tetrasubstituted GHRH analog (Ala2, Gln8, Ala15, Leu27) with ~30-minute half-life (vs ~7 min native GHRH) due to DPP-IV resistance. Lacking DAC's albumin binding, it produces acute pulsatile GH release mimicking physiology, synergizing with GHRPs via complementary cAMP/Ca2+ pathways.

Ipamorelin is the first GHRP with GHRH-like selectivity, binding GHSR-1a (ghrelin receptor) to stimulate pulsatile GH release with EC50 = 1.3 nmol/L and Emax = 85% comparable to GHRP-6, but without ACTH/cortisol elevation even at >200-fold above GH ED50. Lower plasma clearance (5-fold slower than GHRP-6) with ~50% nasal bioavailability.

Sermorelin is the 29-aa minimal bioactive GHRH fragment with full receptor equivalence to 44-aa native GHRH. Previously FDA-approved (Geref, 1990s) for pediatric GH deficiency, it preserves pulsatile GH secretion and hypothalamic feedback. Available via compounding; ~10-20 min half-life requires bedtime dosing.

Tesamorelin is the only FDA-approved GHRH analog (2010), indicated for HIV-associated lipodystrophy. The 44-aa sequence with N-terminal trans-3-hexenoic acid modification stimulates endogenous pituitary GH, reducing visceral adipose tissue 10-18% vs placebo while preserving feedback regulation.

IGF-1 LR3 is a synthetic 83-amino-acid IGF-1 analog with an Arg3 substitution and 13-aa N-terminal extension that reduces IGFBP binding, extending half-life from ~15 min to 20-30 hours. Activates PI3K/Akt/mTOR pathway for protein synthesis while suppressing FoxO-mediated ubiquitin-proteasome degradation via GSK3β inhibition.