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Ipamorelin vs GHRP-2 vs GHRP-6: Comparing Three Ghrelin-Receptor Research Peptides

By The Bionova Club Team

Research use only. Bionova products are sold strictly for in-vitro and laboratory research by qualified professionals. They are not drugs, food, or cosmetics, are not approved by the FDA, and are not for use in people or animals. Nothing in this article is medical advice or a claim about effects in people.

Disclosure: Bionova Club sells ipamorelin and a CJC-1295 (no DAC) + ipamorelin blend, linked below. GHRP-2 and GHRP-6 are discussed here for comparison.

Ipamorelin, GHRP-2 and GHRP-6 are often listed together as "growth hormone secretagogues," and searches such as "ipamorelin vs GHRP-6" suggest they are interchangeable. They do share a receptor and a family history. They also differ in sequence, in length and, most notably, in how selective they appeared in the animal studies that first characterized them.

This guide compares the three by structure, receptor pharmacology and the models in which they were studied. It does not describe outcomes or effects outside those laboratory models. For background on peptide structure in general, see What Are Peptides?

Ipamorelin vs GHRP-2 vs GHRP-6 at a glance

  • Length
    • GHRP-6: 6 amino acids (hexapeptide)
    • GHRP-2: 6 amino acids (hexapeptide)
    • Ipamorelin: 5 amino acids (pentapeptide)
  • Sequence
    • GHRP-6: His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂
    • GHRP-2: D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂
    • Ipamorelin: Aib-His-D-2-Nal-D-Phe-Lys-NH₂
  • Molecular formula (PubChem)
    • GHRP-6: C₄₆H₅₆N₁₂O₆ (CID 4345065)
    • GHRP-2: C₄₅H₅₅N₉O₆ (CID 6918245)
    • Ipamorelin: C₃₈H₄₉N₉O₅ (CID 9831659)
  • Approximate molar mass (free peptide)
    • GHRP-6: about 873.0 g/mol
    • GHRP-2: about 818.0 g/mol
    • Ipamorelin: about 711.9 g/mol
  • Other names
  • Receptor
    • All three: the growth hormone secretagogue receptor (GHS-R1a), now known as the ghrelin receptor

A short history of the GHRP family

GHRP-6: the first well-characterized hexapeptide

In 1984, Bowers and colleagues described a synthetic hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂, now widely known as GHRP-6. They studied it in vitro in a pituitary incubation assay and in vivo in rats, monkeys, lambs and calves, and reported that it released growth hormone (GH) without a concomitant release of LH, FSH, TSH or prolactin in those models (Bowers et al., 1984, Endocrinology). The finding was notable because the peptide was designed, not isolated from tissue, and at the time its natural counterpart was unknown.

GHRP-2: a modified sequence

GHRP-2 belongs to the same synthetic series. Compared with GHRP-6, the N-terminal histidine is replaced by D-alanine and the D-tryptophan at position 2 is replaced by D-2-naphthylalanine (D-2-Nal), an unnatural aromatic amino acid. The C-terminal Ala-Trp-D-Phe-Lys-NH₂ portion is shared. Bowers reviewed the growth hormone-releasing peptides, including GHRP-2, and their place in GH-secretion research in a 1998 overview (Bowers, 1998, Cellular and Molecular Life Sciences).

The receptor and its natural ligand

For more than a decade, the GHRPs were tools in search of an explanation. Bowers's 1998 review noted growing evidence that they mimicked a natural hormone that had not yet been identified. Two discoveries filled the gap:

  • 1996: the receptor. Howard and colleagues cloned a G-protein-coupled receptor expressed in the pituitary and hypothalamus that responds to these secretagogues, the GHS receptor (Howard et al., 1996, Science).
  • 1999: the ligand. Kojima and colleagues identified ghrelin, an acylated peptide from the stomach, as the endogenous ligand of that receptor (Kojima et al., 1999, Nature).

Since then, GHRP-6, GHRP-2 and ipamorelin have been described as synthetic ghrelin-receptor agonists.

Ipamorelin: built for selectivity

Ipamorelin came out of a medicinal-chemistry program at Novo Nordisk. Raun and colleagues described it as a pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH₂, identified within a series of compounds that lack the central Ala-Trp dipeptide found in earlier GHRPs (Raun et al., 1998, European Journal of Endocrinology). Aib is α-aminoisobutyric acid, another unnatural residue.

The same paper is the main source for comparing ipamorelin directly with GHRP-6 and GHRP-2. The models and reported findings were:

  • Primary rat pituitary cells (in vitro). Ipamorelin's GH-releasing potency and efficacy were reported as similar to GHRP-6. Antagonist profiling indicated that it acts through a GHRP-like receptor.
  • Anesthetized rats. Potency and efficacy were again reported as comparable to GHRP-6.
  • Conscious swine. Ipamorelin and GHRP-6 were reported as similar; GHRP-2 showed higher potency but lower maximal efficacy in that model.
  • Hormone specificity in swine. None of the three affected FSH, LH, prolactin or TSH in plasma. GHRP-6 and GHRP-2 were reported to raise ACTH and cortisol. Ipamorelin did not raise ACTH or cortisol beyond levels seen with GHRH stimulation, across the range tested.

On that basis, the authors described ipamorelin as the first GHRP-receptor agonist with a selectivity for GH release similar to that of GHRH. That is a pharmacological description from one research group's rat and swine models, and it should be read as such.

Key differences between the three

Structure

  • Shared core: All three end in D-Phe-Lys-NH₂ and contain unnatural D-amino acids, which are common in designed peptides.
  • GHRP-6 vs GHRP-2: Same length; GHRP-2 swaps the first two residues for D-Ala and D-2-Nal.
  • Ipamorelin vs both: One residue shorter, lacks the Ala-Trp unit, and adds Aib at the N-terminus.

Selectivity in the original animal models

  • GHRP-6 and GHRP-2: Reported to affect ACTH and cortisol in swine in addition to GH.
  • Ipamorelin: Reported as selective for GH release in the same swine model.

Research role today

  • GHRP-6: A reference compound in the historical literature on GH secretagogues.
  • GHRP-2: A related analog that showed higher potency than GHRP-6 in the swine comparison.
  • Ipamorelin: Cited as a selectivity reference, and combined with the GHRH analog CJC-1295 in some research blends.

Where ipamorelin fits in GH-secretagogue research

GHRP-family peptides act at the ghrelin receptor. GHRH analogs such as CJC-1295 and tesamorelin act at a different receptor, the GHRH receptor. Labs that want to study both pathways sometimes work with a combined format. Bionova offers ipamorelin on its own and a CJC-1295 (no DAC) + ipamorelin blend. For a GHRH-analog comparison point, see tesamorelin, or browse the full peptides category.

Key takeaways

  • Ipamorelin, GHRP-2 and GHRP-6 are synthetic agonists of the same receptor, GHS-R1a, the ghrelin receptor.
  • GHRP-6 and GHRP-2 are hexapeptides; ipamorelin is a pentapeptide that lacks their central Ala-Trp unit.
  • The receptor was cloned in 1996 and its natural ligand, ghrelin, was identified in 1999, years after GHRP-6 was first described.
  • In swine, Raun and colleagues (1998) reported that ipamorelin, unlike GHRP-6 and GHRP-2, did not raise ACTH or cortisol above the levels seen with GHRH (Raun et al., 1998).
  • All three are research compounds and are not approved for use in people.

Frequently asked questions

Are ipamorelin, GHRP-2 and GHRP-6 the same thing?

No. They act at the same receptor, but they are different molecules with different sequences and lengths, and they behaved differently in the original selectivity studies.

What does "GHRP" stand for?

Growth hormone-releasing peptide. It is a family name for synthetic peptides designed to act at the receptor now known as the ghrelin receptor.

Is ipamorelin a GHRH analog?

No. Ipamorelin acts at the ghrelin receptor. GHRH analogs such as CJC-1295 and tesamorelin act at the GHRH receptor, a separate target.

Why does selectivity matter in research?

A more selective tool compound makes it easier to attribute an observation to one pathway. That is why Raun and colleagues emphasized the ACTH and cortisol findings in their swine model.

Shop for your research: ipamorelin or the CJC-1295 (no DAC) + ipamorelin blend, for laboratory research. Use code CLUB10 at checkout for 10% off.

References

  1. Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. 1984. https://pubmed.ncbi.nlm.nih.gov/6714155/
  2. Bowers CY. Growth hormone-releasing peptide (GHRP). Cell Mol Life Sci. 1998. https://pubmed.ncbi.nlm.nih.gov/9893708/
  3. Howard AD, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996. https://pubmed.ncbi.nlm.nih.gov/8688086/
  4. Kojima M, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999. https://pubmed.ncbi.nlm.nih.gov/10604470/
  5. Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998. https://pubmed.ncbi.nlm.nih.gov/9849822/
  6. PubChem compound records: GHRP-6 (CID 4345065), https://pubchem.ncbi.nlm.nih.gov/compound/4345065; pralmorelin/GHRP-2 (CID 6918245), https://pubchem.ncbi.nlm.nih.gov/compound/6918245; ipamorelin (CID 9831659), https://pubchem.ncbi.nlm.nih.gov/compound/9831659

For laboratory research use only. Not for human consumption.