What Is Ipamorelin?

Research Overview

Ipamorelin (NNC 26-0161) is a synthetic pentapeptide growth hormone secretagogue with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂, developed by Novo Nordisk in the mid-1990s by systematic modification of GHRP-1. It acts as a highly selective agonist of the GHS-R1a receptor (ghrelin receptor), stimulating potent, pulsatile growth hormone release without affecting ACTH, cortisol, FSH, LH, TSH, or prolactin — even at high multiples of active concentrations.[1][2]

Ipamorelin research spans 8+ indication categories including selective GH secretion, postoperative ileus, bone growth, body composition, insulin secretion, pain modulation, and cancer cachexia. A Phase II clinical trial for POI (n=114, NCT00672074) failed to reach statistical significance, and clinical development was discontinued.[6][4]

Key distinguishing features include: (1) first selective GHS with GHRH-like specificity, (2) no somatotroph desensitization in chronic rodent studies, (3) linear pharmacokinetics in humans (T½ ~2h), and (4) GH-independent adipogenic effects.[1][9]

Structurally, ipamorelin is a non-natural pentapeptide built around the Aib-His-D-2-Nal-D-Phe-Lys-NH₂ scaffold, in which two D-amino acids and one α-aminoisobutyric acid residue confer resistance to enzymatic degradation. Raun and colleagues (1998) reported the original pharmacological characterization, demonstrating in vitro EC₅₀ values of 1.3 ± 0.4 nmol/L for GH release in primary rat pituitary cell cultures and in vivo ED₅₀ values of approximately 80 nmol/kg in rats and 2.3 nmol/kg in swine.[1] The compound was originally developed as a candidate for postoperative ileus and as a tool molecule for studying the ghrelin/GHS-R1a axis.[4]

Ipamorelin sits within a broader family of growth hormone secretagogues that includes CJC-1295 (GHRH analog), sermorelin (GHRH 1–29), and tesamorelin (stabilized GHRH analog). Among these, ipamorelin is unique in acting on the GHS-R1a (ghrelin) receptor rather than the GHRH receptor, a complementary receptor pathway; co-stimulation of GHS-R1a and GHRH-R has been studied in pituitary-cell and rodent models.[1][15] Phase I human pharmacokinetic data (Gobburu et al., 1999) established linear PK with a terminal half-life of ~2 hours and SC₅₀ of 214 nmol/L.[2]