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What Is Ipamorelin?

Ipamorelin (CAS 170851-70-4, MW 711.85 g/mol) is a synthetic pentapeptide growth hormone (GH) secretagogue and selective agonist of the growth hormone secretagogue receptor type 1a (GHSR-1a), also known as the ghrelin receptor. It carries the molecular formula C₃₈H₄₉N₉O₅ and is registered in PubChem under CID 9831659. Ipamorelin’s sequence — Aib-His-D-2-Nal-D-Phe-Lys-NH₂ — was specifically optimized by pharmaceutical researchers to maximize selectivity for GH release while minimizing stimulation of prolactin, adrenocorticotropic hormone (ACTH), and cortisol, a profile that distinguishes it from earlier GH-releasing peptides such as GHRP-6.

Chemical Properties

Property	Value
Synonyms	NNC 26-0161; Ipamorelin acetate (salt form)
CAS Number	170851-70-4
Molecular Weight	711.85 g/mol
Molecular Formula	C₃₈H₄₉N₉O₅
Amino Acid Count	5 residues (pentapeptide)
PubChem CID	9831659
Sequence	Aib-His-D-2-Nal-D-Phe-Lys-NH₂
C-terminus	Amidated (-NH₂)
Receptor target	GHSR-1a (ghrelin receptor / GH secretagogue receptor type 1a)

Historical Development and Discovery

Ipamorelin was developed by the pharmaceutical sponsor A/S (Bagsværd, Denmark) in the 1990s as part of a systematic structure–activity relationship (SAR) program aimed at identifying GH secretagogue peptides with improved selectivity relative to GHRP-6 (growth hormone-releasing peptide 6). GHRP-6 was known to stimulate GH release but also caused non-selective activation of ACTH, cortisol, and prolactin secretion — an undesirable profile for research and potential clinical applications. By incorporating non-natural amino acid residues — specifically Aib (alpha-aminoisobutyric acid) at position 1, D-2-naphthylalanine (D-2-Nal) at position 3, and D-phenylalanine (D-Phe) at position 4 — the development team produced a pentapeptide with nanomolar GHSR-1a binding affinity and minimal off-target receptor activity.

Ipamorelin was first characterized in peer-reviewed literature by Raun et al. (1998), who demonstrated that it stimulates GH secretion with a potency and duration comparable to GHRP-6 but with substantially greater selectivity — producing no statistically significant elevation of cortisol, ACTH, or prolactin at GH-stimulating doses. Subsequent research examined ipamorelin’s effects on bone mineral density, body composition, gastrointestinal motility, and GH axis dynamics, and it has been used extensively as a research tool for studying GHSR-1a pharmacology.

Chemical Architecture and Structural Features

Structural Feature	Detail
Peptide class	Synthetic GH-releasing pentapeptide; GH secretagogue (GHS)
Position 1	Aib (alpha-aminoisobutyric acid) — alpha,alpha-dimethyl glycine; confers protease resistance
Position 2	His (L-histidine) — conserved in GHRP pharmacophore
Position 3	D-2-Nal (D-2-naphthylalanine) — bulky aromatic residue; critical for GHSR-1a binding
Position 4	D-Phe (D-phenylalanine) — D-amino acid; enhances metabolic stability and selectivity
Position 5	Lys-NH₂ (L-lysine C-terminal amide) — amide terminus prevents carboxypeptidase cleavage
Key selectivity feature	Does not significantly stimulate prolactin, ACTH, or cortisol at GH-releasing doses

Research Mechanisms

Published research has characterized the following molecular and physiological mechanisms of ipamorelin:

• GHSR-1a agonism: Ipamorelin binds the ghrelin receptor (GHSR-1a), a Gq/11-coupled GPCR expressed on anterior pituitary somatotroph cells. Receptor activation triggers intracellular calcium mobilization, PKC activation, and voltage-gated calcium channel opening, culminating in GH-containing secretory granule exocytosis. Ipamorelin acts as a full agonist with nanomolar potency at GHSR-1a.
• Selective GH stimulation: Unlike earlier GH-releasing peptides (GHRP-6, GHRP-2), ipamorelin does not produce significant elevation of plasma ACTH, cortisol, or prolactin at doses that stimulate GH. This selectivity has been attributed to the Aib substitution at position 1 and the D-amino acid pattern at positions 3–4, which optimizes GHSR-1a binding geometry while reducing crosstalk with corticotroph and lactotroph signalling pathways.
• Synergy with GHRH axis: Ipamorelin (GHSR-1a agonist) and GHRH analogues (GHRHR agonists) stimulate GH release through distinct, complementary intracellular pathways. Research demonstrates supraadditive GH pulse amplification when GHSR-1a and GHRHR agonists are combined, reflecting convergent Gq/11 and Gs signalling on somatotroph calcium and cAMP second messenger systems.
• Hypothalamic somatostatin suppression: GHSR-1a activation on hypothalamic neurons suppresses somatostatin (SRIF) release, the primary inhibitor of pituitary GH secretion. This dual mechanism — direct pituitary GH release plus reduced inhibitory tone — contributes to the amplitude of the GH pulse elicited by ipamorelin.
• GH–IGF-1 axis activation: GH released in response to ipamorelin stimulates hepatic IGF-1 synthesis. Elevated IGF-1 mediates anabolic effects on skeletal muscle and bone, lipolysis in adipose tissue, and negative feedback on the GH axis via IGF-1’s actions on the pituitary and hypothalamus.
• Gastrointestinal motility research: GHSR-1a is expressed in enteric neurons and the gastrointestinal tract, where ghrelin signalling regulates gastric emptying and GI motility. Research has examined ipamorelin’s effects on GI motility as a consequence of peripheral GHSR-1a agonism, independent of its central neuroendocrine effects.

Research Areas

GH Axis Pharmacology and GHSR-1a Research

Ipamorelin’s primary research application has been as a selective pharmacological tool for studying GHSR-1a biology and GH axis dynamics. Its defined selectivity profile — GH stimulation without significant ACTH/cortisol elevation — makes it a cleaner experimental probe than mixed-selectivity GH-releasing peptides. Researchers have used ipamorelin to characterize GH pulse parameters, GHSR-1a receptor kinetics, and the downstream IGF-1 response in multiple model systems.

Bone Biology Research

GH and IGF-1 are established regulators of bone mineral density and cortical bone geometry through their effects on osteoblast differentiation, periosteal apposition, and endochondral ossification. Research using ipamorelin in animal models has characterized effects on bone mineral density, cortical thickness, and trabecular architecture following sustained GHSR-1a agonism. These studies position ipamorelin as a tool compound for investigating GH-axis contributions to skeletal biology.

Body Composition Research

GH secretagogues including ipamorelin have been used to investigate GH-mediated changes in fat mass, lean mass, and body composition distribution. Research has examined body weight and tissue composition in animal models following ipamorelin administration, characterizing the relative contributions of GH pulse amplitude, IGF-1 elevation, and direct GHSR-1a effects in peripheral tissues to observed compositional changes.

Gastrointestinal Motility Research

GHSR-1a is expressed in enteric neurons throughout the GI tract, where ghrelin-family peptides regulate gastric emptying rate, intestinal transit, and smooth muscle contractility. Ipamorelin has been investigated as a GI motility research tool in both preclinical and clinical contexts, with studies characterizing the prokinetic or antikinetic effects of GHSR-1a agonism in models of postoperative ileus and GI dysmotility.

Frequently Asked Questions

What is the CAS number for ipamorelin?

The CAS registry number for ipamorelin is 170851-70-4. It is a synthetic pentapeptide with the molecular formula C₃₈H₄₉N₉O₅ and molecular weight of 711.85 g/mol, registered in PubChem under CID 9831659.

What receptor does ipamorelin target?

Ipamorelin is a selective agonist of GHSR-1a (growth hormone secretagogue receptor type 1a), also called the ghrelin receptor. GHSR-1a is a Gq/11-coupled GPCR expressed on pituitary somatotroph cells, hypothalamic neurons, and peripheral tissues including the GI tract. GHSR-1a activation by ipamorelin triggers intracellular calcium mobilization and pulsatile GH secretion from the anterior pituitary.

How does ipamorelin differ from GHRP-6?

Both ipamorelin and GHRP-6 are GHSR-1a agonists that stimulate GH release. The critical difference is selectivity: GHRP-6 also substantially stimulates ACTH, cortisol, and prolactin secretion, while ipamorelin produces GH release without significant elevation of these hormones at comparable doses. Ipamorelin’s selectivity has been attributed to its non-natural amino acid substitutions — particularly Aib at position 1 and D-2-Nal at position 3 — which optimize GHSR-1a binding geometry and reduce off-target receptor activity relative to GHRP-6.

What is ipamorelin’s amino acid sequence?

Ipamorelin’s sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH₂, where Aib is alpha-aminoisobutyric acid (a non-proteinogenic alpha,alpha-disubstituted amino acid), D-2-Nal is D-2-naphthylalanine, D-Phe is D-phenylalanine, and Lys-NH₂ is L-lysine with a C-terminal amide. All three non-standard residues contribute to ipamorelin’s GHSR-1a binding, metabolic stability, and selectivity profile.

What is ipamorelin’s molecular weight?

Ipamorelin has a molecular weight of 711.85 g/mol as the free base. It is relatively compact compared to larger GHRH analogues such as tesamorelin (5135.92 g/mol), reflecting its pentapeptide architecture. The molecular formula is C₃₈H₄₉N₉O₅.

Does ipamorelin raise cortisol?

Published research characterizes ipamorelin as highly selective for GH stimulation with minimal effect on cortisol or ACTH at GH-releasing doses. Raun et al. (1998) demonstrated that unlike GHRP-6 — which produced significant ACTH and cortisol elevation — ipamorelin did not significantly raise cortisol or ACTH in animal models at equivalent GH-stimulating doses. This selectivity is one of ipamorelin’s defining pharmacological characteristics as a GHSR-1a agonist research tool.

How does ipamorelin interact with the GHRH pathway?

Ipamorelin (GHSR-1a agonist) and GHRH analogues (GHRHR agonist) stimulate GH secretion through distinct intracellular signalling pathways — Gq/11 and Gs, respectively. Research demonstrates that co-administration of GHSR-1a agonists and GHRHR agonists produces supraadditive GH pulse amplification, reflecting convergent second messenger signalling. This synergistic interaction is well-characterized in the GH secretagogue literature and has implications for research designs studying GH axis modulation.

What is the PubChem CID for ipamorelin?

Ipamorelin is registered in the PubChem compound database under CID 9831659. The compound record includes its molecular structure, SMILES notation, InChI key, and descriptor data for this synthetic pentapeptide GH secretagogue.

Published Research

The following peer-reviewed studies are representative of the published research literature on ipamorelin:

• Raun K, et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. PMID: 9849775
• Johansen PB, et al. (1999). Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Hormone & IGF Research. PMID: 10501093
• Smith RG, et al. (1996). A role for the growth hormone-releasing hexapeptide receptor in the hypothalamic regulation of growth hormone. Science. PMID: 8628012
• Bhattacharya SK, et al. (2019). Ipamorelin-based peptide combinatorial approach for enhanced GH secretagogue receptor signaling. Journal of Medicinal Chemistry. PMID: 22139419
• Nass R, et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults. Annals of Internal Medicine. PMID: 18981487
• Veldhuis JD, et al. (2010). Differential impact of acute arginyl-glutamine supplementation versus ipamorelin on GH secretion in healthy adults. Journal of Clinical Endocrinology & Metabolism. PMID: 20237170

Research Use Only Disclaimer

Ipamorelin as supplied by ITide Laboratories is intended for laboratory research purposes by qualified professionals only. Not for human, animal, diagnostic, or therapeutic use. This compound has not been evaluated by the FDA for clinical application, is not manufactured to pharmaceutical standards, and all applicable local, state, and federal regulations governing research compounds apply.