Ipamorelin

Ipamorelin (sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2; CAS 170851-70-4; molecular formula C38H49N9O5; molecular weight 711.86) is a synthetic pentapeptide growth hormone secretagogue (GHS) developed at Novo Nordisk in the mid-1990s and disclosed in a 1998 paper by Raun and colleagues. Ipamorelin is a selective agonist of the growth hormone secretagogue receptor 1a (GHS-R1a, the ghrelin receptor), the receptor through which the endogenous peptide ghrelin and the small-molecule MK-0677 also act. Selective activation of GHS-R1a triggers pulsatile growth hormone (GH) release from the anterior pituitary without the concurrent stimulation of cortisol, ACTH, or prolactin that complicates the pharmacology of older GHS compounds (GHRP-2, GHRP-6, hexarelin). The selectivity profile is the basis on which Ipamorelin remains the most-cited research-grade GHS in the post-2010 literature. The compound was advanced through Phase 2 trials by Helsinn Therapeutics for postoperative ileus before development was discontinued for commercial reasons. Reported preclinical activities include dose-dependent GH pulse induction, increased IGF-1 axis activity over multi-day administration, modest effects on appetite (smaller than ghrelin's), and accelerated bone mineral density gains in osteopenic rodent models. Plasma half-life is approximately 2 hours, with subcutaneous administration producing predictable absorption. The compound is not approved by any regulatory authority for human or veterinary use. The literature base is solid for the basic pharmacology but limited for long-term safety data in humans; the clinical record is principally from a single short-term ileus indication.