Ipamorelin — Molecular Weight, Formula, Sequence & Half-Life Reference

01What is Ipamorelin?

Ipamorelin is a five-residue growth hormone secretagogue acting at the GHS-R1a (ghrelin) receptor. Three of its five positions are occupied by non-proteinogenic residues — 2-aminoisobutyric acid, D-2-naphthylalanine and D-phenylalanine — which is why no valid all-standard one-letter sequence representation exists for it, and why any database entry that prints one should be treated with suspicion.

The selectivity claim is the compound's actual scientific signature. In the original characterisation work ipamorelin produced growth hormone release comparable to earlier GHRPs while leaving ACTH and cortisol at or near baseline at effective doses — a cleaner endocrine profile than GHRP-2 or GHRP-6, and the reason it remains widely referenced despite never reaching approval.

Its clinical history is short and worth stating plainly: development advanced into trials for postoperative ileus and then stopped. The often-quoted two-hour half-life comes from a single 1999 intravenous study in healthy young men, and does not transfer to subcutaneous administration or to other populations.

02Molecular information

03Amino acid sequence

Structural modifications

Three deliberate departures from a natural peptide. Position 1 is Aib (alpha-aminoisobutyric acid, 2-methylalanine), an achiral non-proteinogenic residue with a quaternary alpha-carbon that constrains backbone conformation and blocks aminopeptidase cleavage. Position 3 is D-2-Nal (D-3-(2-naphthyl)alanine), a bulky D-configured aromatic residue. Position 4 is D-Phe (D-phenylalanine). Position 2 is standard L-histidine and position 5 is standard L-lysine. The C-terminus is a primary carboxamide (-NH2), not a free acid. There are no cysteines and therefore no disulfide bonds, no cyclisation, no N-terminal acetylation, and no fatty-acid or PEG conjugation. The D-residues and Aib together are what confer protease resistance; FDA has noted that these unnatural amino acids also complicate analytical characterisation of the substance.

04Pharmacokinetic information

Half-life context

The single authoritative human value comes from Gobburu et al., Pharmaceutical Research 1999, a phase 1 pharmacokinetic-pharmacodynamic study in healthy male volunteers. Eight subjects per dose level received 15-minute intravenous infusions at five escalating rates (4.21, 14.02, 42.13, 84.27 and 140.45 nmol/kg). Reported parameters: terminal half-life 2 hours, clearance 0.078 L/h/kg, steady-state volume of distribution 0.22 L/kg, with dose-proportional kinetics across the range. These are intravenous values in healthy young men; no authoritative subcutaneous human pharmacokinetic dataset was retrieved, and subcutaneous absorption would be expected to make the observed half-life absorption-rate-limited rather than elimination-limited, so the 2-hour figure should not be assumed to transfer to that route. Effect duration is a separate and shorter quantity: the same study modelled a single growth hormone release episode peaking at 0.67 hours, with an SC50 of 214 nmol/L and maximum GH production rate of 694 mIU/L/h, and noted that pharmacodynamic variability between subjects exceeded pharmacokinetic variability. Preclinical potency data from Raun et al. 1998 are dose-response, not half-life, values: EC50 1.3 +/- 0.4 nmol/L in rat pituitary cells, ED50 80 +/- 42 nmol/kg in anaesthetised rats, and ED50 2.3 +/- 0.03 nmol/kg in conscious swine. Do not collapse these to a single cross-species number.

05Research focus

Primary research areas

• selective growth hormone secretagogue pharmacology
• GHS-R1a / ghrelin receptor agonism
• postoperative ileus and gastrointestinal motility
• GH release without ACTH or cortisol elevation
• phase 1 pharmacokinetic-pharmacodynamic modelling

Research context

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue developed at Novo Nordisk and first described by Raun and colleagues in 1998 [1]. Its sequence, Aib-His-D-2-Nal-D-Phe-Lys-NH2, contains three non-proteinogenic elements - alpha-aminoisobutyric acid at position 1, D-2-naphthylalanine at position 3, and D-phenylalanine at position 4 - plus a C-terminal amide, together conferring protease resistance. It acts as an agonist at the growth hormone secretagogue receptor GHS-R1a, the ghrelin receptor, stimulating growth hormone release from the pituitary [1]. Its defining reported property is selectivity. In the original characterisation, ipamorelin released growth hormone with an EC50 of 1.3 +/- 0.4 nmol/L in rat pituitary cells, an ED50 of 80 +/- 42 nmol/kg in anaesthetised rats and 2.3 +/- 0.03 nmol/kg in conscious swine, yet produced no significant ACTH or cortisol release even at doses exceeding the GH ED50 by more than 200-fold - a selectivity profile the authors described as resembling GHRH and contrasting with GHRP-6 and GHRP-2, both of which stimulated ACTH and cortisol in the same experiments [1]. Human pharmacology is limited to early-phase work. Gobburu and colleagues characterised intravenous pharmacokinetics and GH response in healthy male volunteers, reporting a terminal half-life of 2 hours, clearance of 0.078 L/h/kg, steady-state volume of distribution of 0.22 L/kg, dose-proportional kinetics, and a single modelled GH release episode peaking at 0.67 hours [2]. The furthest clinical development reached was a phase 2 trial sponsored by Helsinn Therapeutics, NCT01280344, enrolling 320 patients to test intravenous ipamorelin at 0.03 mg/kg twice daily, 0.06 mg/kg twice daily, and 0.06 mg/kg three times daily against placebo for recovery of gastrointestinal function after bowel resection with primary anastomosis; the trial ran from 2011 to 2014 and completed, but results were never posted [4]. FDA's 2024 review of the compound states that this single postoperative-ileus study showed no statistically significant benefit and that development was discontinued [3].

06Research evidence and limitations

Regulatory status

Investigational; never approved in any jurisdiction. Originated at Novo Nordisk A/S and later taken to phase 2 by Helsinn Therapeutics for postoperative gastrointestinal dysmotility; development was discontinued. In an FDA briefing document dated 19 August 2024, prepared for the Pharmacy Compounding Advisory Committee, FDA evaluated ipamorelin free base and ipamorelin acetate for the 503A bulk drug substances list and recommended against adding either, citing inadequate physicochemical characterisation, absence of a USP monograph or approved drug product, missing impurity and endotoxin data on available certificates of analysis, immunogenicity and aggregation concerns for injectable use, possible reproductive toxicity, potential behaviourally reinforcing properties of ghrelin receptor agonists, and no credible evidence of effectiveness [3]. Ipamorelin acetate also appears in FDA's Category 2 listing of bulk drug substances that may present significant safety risks in the 503B outsourcing-facility context, added 29 September 2023. Ipamorelin is explicitly named on the WADA Prohibited List under section S2 as a growth hormone secretagogue, prohibited at all times, both in and out of competition [5].

07Research material and sourcing notes

Reported research-use reconstitution information

Manufacturer technical documentation (Cayman Chemical product insert, item 39813, ipamorelin acetate, purity >=98 percent, research use only): supplied as a solid; solubility approximately 30 mg/mL in ethanol, approximately 20 mg/mL in DMSO, approximately 20 mg/mL in DMF, and approximately 10 mg/mL in PBS at pH 7.2. The insert advises purging organic solvents with inert gas, then diluting stock into aqueous buffer or saline such that residual organic solvent is insignificant, and states that direct dissolution in aqueous buffer is possible but that aqueous solutions should not be stored more than one day. Separately, FDA's 2024 bulk-substance evaluation observed that ipamorelin free base has limited aqueous solubility, which it considered problematic for a proposed 2 mg/mL injectable formulation - a relevant contrast, since the acetate salt is the more soluble form. Laboratory handling information only; no dosing guidance is given or implied.

Reported storage and stability information

Manufacturer technical documentation (Cayman Chemical insert, item 39813): store the solid at -20 C, where it is stated to be stable for at least 4 years. Aqueous solutions are not recommended for storage beyond one day per the same insert. No pharmacopoeial monograph exists for ipamorelin - FDA's 2024 evaluation states explicitly that there is no USP monograph and no FDA-approved drug product - so there is no compendial storage specification. Source type: supplier technical insert plus an FDA regulatory evaluation document.

Identity and sourcing notes

Ipamorelin is almost always supplied as the acetate salt rather than the free base, and the acetate stoichiometry is usually unfixed and undeclared, so nominal milligram content overstates peptide content. Residual trifluoroacetate from reverse-phase purification is a common and frequently undeclared counter-ion; a COA should state the counter-ion and, ideally, quantify residual TFA. FDA's 2024 evaluation specifically observed that certificates of analysis it reviewed lacked tests, limits and results for impurities and for bacterial endotoxins, so the presence of a COA alone is not evidence of adequate characterisation. Because Aib, D-2-Nal and D-Phe are non-proteinogenic, routine amino acid analysis will not resolve them and standard sequencing approaches can be confounded - FDA has noted that these unnatural residues complicate characterisation. Identity should therefore rest on high-resolution mass spectrometry against the C38H49N9O5 free-base mass together with RP-HPLC purity at a stated threshold, and ideally chiral verification that positions 3 and 4 are the D-enantiomers, since the L-diastereomers are plausible synthesis impurities with different pharmacology. Aggregation is a specific documented concern for this peptide class. Ipamorelin is also very commonly sold pre-blended with CJC-1295 forms, in which case neither component's identity or ratio can be assumed from the label. Informational only.

08References and evidence

Primary sources

1. Ipamorelin, the first selective growth hormone secretagogueprimary literatureRaun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH — European Journal of Endocrinology, 1998;139(5):552-561
2. Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteersclinical trialGobburu JVS, Agerso H, Jusko WJ, Ynddal L — Pharmaceutical Research, 1999;16:1412-1416
3. FDA Evaluation of Ipamorelin-related Bulk Drug Substances (Pharmacy Compounding Advisory Committee briefing document)regulatoryU.S. Food and Drug Administration — FDA, 19 August 2024
4. Safety and Efficacy of Ipamorelin Compared to Placebo for the Recovery of Gastrointestinal Function (NCT01280344)clinical trialHelsinn Therapeutics (U.S.), Inc. — ClinicalTrials.gov, phase 2, 320 participants, 2011-2014, no results posted
5. The 2026 Prohibited List, International Standard - section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics)regulatoryWorld Anti-Doping Agency — WADA, in force 1 January 2026

Chemical and molecular databases

• PubChem CID 9831659 (Ipamorelin, C38H49N9O5)
• NCATS Inxight Drugs - IPAMORELIN (UNII Y9M3S784Z6, CAS 170851-70-4, MW 711.853)
• Cayman Chemical item 39813 product insert, ipamorelin (acetate) (supplier documentation - solubility and storage only)
• FDA - Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (Category 2)
• WADA Prohibited List landing page

09Related compounds

• GHRP-2Direct comparator in the original 1998 characterisation, where it released GH but also raised ACTH and cortisol, unlike ipamorelin.Reference page in preparation
• GHRP-6The other head-to-head comparator in Raun et al.; its ACTH and cortisol response defined the selectivity contrast ipamorelin was named for.Reference page in preparation
• HexarelinEarlier GHRP-class secretagogue acting at the same GHS-R1a receptor, named alongside ipamorelin on the WADA Prohibited List.Reference page in preparation
• MK-677 (Ibutamoren)Orally active, long-acting non-peptide agonist of the same ghrelin receptor, representing the alternative pharmaceutical route to the same target.Reference page in preparation
• CJC-1295 (with DAC)Acts on the complementary GHRH receptor rather than GHS-R1a, and is the compound most often co-formulated with ipamorelin in commerce.

10Frequently asked questions