C tier · mixed
Its selectivity for GH release without ACTH, cortisol or prolactin elevation is genuinely well demonstrated in preclinical work, but the only published human efficacy trial missed its primary endpoint and no phase 3 efficacy data exist for any indication.
ipamorelin
Ipamorelin is a pentapeptide agonist of the ghrelin receptor (GHS-R1a) reported as the first growth hormone secretagogue with GH selectivity comparable to GHRH itself, without the ACTH and cortisol release seen with earlier GHRPs. Its clinical development was discontinued after a phase 2 trial in postoperative ileus failed to meet its primary endpoint, and FDA has stated it has not identified data supporting effectiveness for any proposed use.
// we supply this one
available as a research reagent
≥ 99% HPLC · lyophilised powder · batch certificate published. Grade C above is our own and is not adjusted because we stock it.
the explanation
Ipamorelin is a very short five-amino-acid peptide that copies the hunger hormone ghrelin to trigger growth hormone release, and unlike its older relatives it does this without also raising stress hormones. The catch is that the one real human trial, in patients recovering from bowel surgery, did not work, and drug development was abandoned afterwards.
regulatory status
Not approved; rejected for compounding
Never approved anywhere; the Pharmacy Compounding Advisory Committee voted 0 yes / 12 no / 1 abstain against including both ipamorelin free base and ipamorelin acetate on the 503A Bulks List on 29 October 2024, and FDA stated it had not identified data supporting effectiveness for growth hormone deficiency or postoperative ileus.
how it works · proposed mechanism
Ipamorelin was designed to isolate the growth hormone effect of the ghrelin receptor from everything else that receptor does.
Ghrelin receptor, not GHRH
Ipamorelin binds GHS-R1a, the same receptor as endogenous ghrelin, which is a completely separate receptor from the GHRH receptor targeted by sermorelin and tesamorelin. This is why the two classes are studied in combination.
Selectivity is the defining claim
Raun 1998 found ipamorelin did not release ACTH or cortisol at levels significantly different from GHRH stimulation, even at 200 times the GH ED50, and did not affect FSH, LH, prolactin or TSH in swine. Earlier GHRPs such as GHRP-6 and GHRP-2 raised ACTH and cortisol at comparable GH doses.
Unnatural residues resist proteases
The pentapeptide incorporates aminoisobutyric acid, D-2-naphthylalanine and D-phenylalanine, none of which are standard L-amino acids. This blocks ordinary peptidase recognition and yields an unusually long terminal half-life of about 2 hours for so small a peptide.
The clinical target was the gut
Ghrelin receptor activation stimulates gastric motility, so the only phase 2 programme targeted postoperative ileus rather than growth hormone deficiency. That trial produced a 7.3-hour reduction in time to tolerating solid food, which was not statistically significant.
what’s reported
evidence shape
5 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The only published efficacy trial, a 114-patient phase 2 study in postoperative ileus, missed its primary endpoint and every secondary endpoint, after which clinical development was discontinued entirely. FDA's 2024 review also found no acute toxicity, repeat-dose toxicity, genotoxicity or carcinogenicity studies, no subcutaneous pharmacokinetic data at all, and noted the free base is so water-insoluble (0.0032 mg/mL) that it cannot be formulated at the concentration typically proposed.
key published findings
- Human RCT (Beck 2014, n=114 adults undergoing small or large bowel resection): prospective multicentre randomised double-blind placebo-controlled phase 2 of IV ipamorelin 0.03 mg/kg twice daily on postoperative days 1-7; median time to tolerating a standardised solid meal was 25.3 h versus 32.6 h on placebo, a 7.3-hour difference that was not statistically significant, with no significant differences in time to first bowel movement, discharge readiness or length of stay.
- Human PK/PD study (Gobburu, Pharmaceutical Research 1999): eight healthy male subjects at each of five 15-minute IV infusion rates (4.21 to 140.45 nmol/kg) showed linear pharmacokinetics and a terminal half-life of approximately 2 hours, with no adverse events attributed to ipamorelin.
- Preclinical (Raun, European Journal of Endocrinology 1998): in primary rat pituitary cells ipamorelin showed potency and efficacy similar to GHRP-6 (EC50 1.3 vs 2.2 nmol/L); in conscious swine it did not release ACTH or cortisol significantly above GHRH stimulation even at 200-fold the GH ED50 and did not alter FSH, LH, prolactin or TSH, establishing it as the first GHRP-receptor agonist with GHRH-like GH selectivity.
- Regulatory review (FDA PCAC briefing 2024): FDA identified no acute, repeat-dose, genotoxicity or carcinogenicity studies, no subcutaneous route pharmacokinetic data for any indication, and only 2 non-serious FAERS reports through 30 September 2023.
- Regulatory review (FDA PCAC briefing 2024): ipamorelin free base water solubility is 0.0032 mg/mL, which FDA stated makes it 'impossible to formulate the proposed injectable dosage form at the concentration of 2 mg/mL'; ipamorelin acetate is soluble at 5 mg/mL.
limitations of the evidence
- Every published human study used the intravenous route; no pharmacokinetic, pharmacodynamic or safety data exist for subcutaneous administration.
- There is no phase 3 efficacy data for any indication and no trial has ever measured body composition, strength or metabolic outcomes in humans.
- The nonclinical toxicology package is essentially absent, so immunogenicity, reproductive toxicity and carcinogenicity risk are uncharacterised rather than reassuring.
identity
| full name | Aib-His-D-2-Nal-D-Phe-Lys-NH2, a selective growth hormone secretagogue receptor agonist |
| category | Growth Hormone |
| modality | peptide |
| formula | C38H49N9O5 |
| molar mass | 711.87 g/mol |
| cas | 170851-70-4 |
| half-life | ~2 h terminal (IV, healthy men; Gobburu 1999) |
| sequence | Aib-His-D-2-Nal-D-Phe-Lys-NH2 |
laboratory handling
| storage | Ipamorelin acetate lyophilised powder is reported stable up to 4 years at -20°C with 2-8°C storage recommended for shorter periods; the free base is stable roughly 3 weeks at room temperature when desiccated, with storage below -18°C recommended. Reconstituted solution is held at 2-8°C, protected from light, and not refrozen. |
| solubility | The acetate salt dissolves in water at about 5 mg/mL and is the form used in laboratory settings, typically reconstituted with bacteriostatic or sterile water; the free base is effectively insoluble in water at 0.0032 mg/mL and requires organic solvent. |
| co-studied with | Ipamorelin is the GHS-R1a half of the classic GHRH-plus-GHRP co-study design, paired in the literature with GHRH-receptor agonists on the rationale that the two receptors converge on somatotroph GH release through separate second-messenger pathways and produce more than additive output. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
5 citedU.S. Food and Drug Administration · 2024 · official
U.S. Food and Drug Administration · 2024 · official
PubChem, National Center for Biotechnology Information (CID 9831659) · 2024 · official
Pharmaceutical Research · 1999 · peer-reviewed
European Journal of Endocrinology · 1998 · preclinical
others in Growth Hormone