Ipamorelin

Origin and Structure of Ipamorelin

Ipamorelin is a synthetic pentapeptide with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂, designed as a selective growth hormone secretagogue (GHS). The peptide was developed at Novo Nordisk laboratories and first described in the literature in 1998 as the first truly selective GHS.

The structure of Ipamorelin contains three non-natural amino acids: alpha-aminoisobutyric acid (Aib) at position 1, D-2-naphthylalanine (D-2-Nal) at position 3, and D-phenylalanine (D-Phe) at position 4. The presence of D-amino acids and the Aib residue confer high protease resistance, while C-terminal amidation (-NH₂) further stabilizes the peptide chain. These modifications make Ipamorelin one of the most selective GH secretagogues, which in animal models does not elicit significant ACTH, cortisol, or prolactin release.

Mechanism of Action

Ipamorelin acts as an agonist of the growth hormone secretagogue receptor type 1a (GHS-R1a), also known as the ghrelin receptor. This receptor is expressed on somatotrophs of the anterior pituitary, where it mediates stimulation of growth hormone (GH) release.

GHS-R1a activation by Ipamorelin initiates a Gq protein-dependent signaling pathway, leading to phospholipase C (PLC) activation and generation of inositol trisphosphate (IP3) and diacylglycerol (DAG). This is a distinct mechanism from the GHRH-activated pathway, which operates through the GHRH-R receptor coupled to Gs protein, activating the cAMP/PKA cascade.

The key feature of Ipamorelin, documented in porcine and rat models, is selectivity for GH release. Unlike older secretagogues (e.g., GHRP-6, GHRP-2), Ipamorelin does not cause significant ACTH or cortisol secretion stimulation. This selectivity, combined with a different signaling pathway from CJC-1295 NO DAC, provides the scientific rationale for combining both peptides, available as the CJC-1295 NO DAC + Ipamorelin blend.

Research Overview

Discovery and characterization of Ipamorelin

Raun, Hansen, Johansen, et al. published in 1998 in European Journal of Endocrinology (139(5):552-561) the landmark paper presenting Ipamorelin as the first selective growth hormone secretagogue ^[1]. Studies in rat and porcine models demonstrated that Ipamorelin stimulates GH release without significant increases in ACTH, cortisol, or prolactin.

Selectivity of growth hormone release

In the porcine model (Raun et al., 1998) ^[1], Ipamorelin administration produced dose-dependent GH increases without changes in ACTH, cortisol, prolactin, FSH, or LH levels. For comparison, GHRP-6 caused parallel elevation of GH and ACTH/cortisol. The selectivity stems from the peptide's receptor properties.

GHRH and GHS pathway synergy

Bowers, Momany, Reynolds, and Hong (1984) described in Endocrinology (114(5):1537-1545) a new hexapeptide capable of specific GH release ^[2]. Subsequent studies confirmed that simultaneous activation of the GHRH-R/cAMP/PKA and GHS-R1a/IP3/DAG pathways produces synergistic GH release several-fold greater than the sum of individual effects.

Comparison with CJC-1295 NO DAC

Ipamorelin and CJC-1295 NO DAC (Mod GRF 1-29) act on the somatotropic axis through two independent receptor pathways. Ipamorelin activates the GHS-R1a (ghrelin) receptor, while CJC-1295 NO DAC binds to the GHRH-R receptor. A ready-made blend of both peptides is available as CJC-1295 NO DAC + Ipamorelin.

Stability and Storage

Ipamorelin is supplied as a lyophilized powder with purity above 98% (RP-HPLC). Store in dry form at -20°C to -80°C (stability at least 24 months). After reconstitution in sterile water, store at 2-8°C and use within 30 days. C-terminal amidation (Lys-NH₂) increases resistance to carboxypeptidase degradation. Avoid repeated freeze-thaw cycles.

Intended Use

This product is a chemical raw material intended exclusively for in vitro research, scientific, and analytical applications. It is not intended for human or veterinary use, including for diagnostic, therapeutic, prophylactic, or nutritional purposes.

Handling

• Work in laboratory conditions consistent with Good Laboratory Practice (GLP) principles.
• Use appropriate personal protective equipment: nitrile gloves, safety goggles, lab coat.
• Avoid inhalation of dust and contact with skin or mucous membranes.
• Work in a well-ventilated area.

Regulatory Classification

This product is not classified as a hazardous substance under CLP Regulation (EC) No 1272/2008. It is offered as a chemical reagent within the framework of applicable European Union chemical substances regulations (REACH, CLP). It does not constitute a medicinal product, dietary supplement, medical device, or cosmetic within the meaning of applicable laws.

Disposal

Unused material should be disposed of in accordance with local regulations on chemical waste. Under laboratory conditions: neutralize and dispose with laboratory waste streams. Do not discharge into sewage systems.

Regulatory Information

This product is offered in accordance with applicable European Union regulations on chemical substances (REACH, CLP) and Polish law governing the trade of chemical reagents and research materials. Full terms of sale and product classification are set out in the Terms of Service.

By placing an order, the Customer confirms having read the above information and accepts the provisions of the Terms.

Safety Contact

For questions regarding handling or regulatory information: [email protected].