Pentapeptide GHSR-1a Agonist (Ghrelin Mimetic, GHRP Class)

Ipamorelin

Also Known As: NNC 26-0161, Ipamorelin acetate

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) synthesised by the Novo Nordisk peptide-discovery programme in the late 1990s under the development code NNC 26-0161 by structural variation of GHRP-1, with the explicit goal of dissociating GH-releasing activity from the cortisol- and prolactin-stimulating side effects characteristic of earlier GHRPs (Raun 1998). Mechanistically it acts at the growth-hormone-secretagogue receptor type 1a (GHSR-1a) — the ghrelin receptor — on pituitary somatotrophs, evoking a discrete pulsatile release of endogenous growth hormone (GH). Its defining pharmacological property is a GH-release selectivity profile similar to GHRH itself: without measurable elevation of ACTH, cortisol, prolactin, FSH, LH or TSH at GH-effective doses. Within the GHRP class this distinguishes ipamorelin sharply from hexarelin (off-target CD36 engagement), GHRP-6 (cortisol and prolactin elevation), and GHRP-2 (ACTH and cortisol elevation). The Helsinn Therapeutics clinical programme for post-operative ileus (NCT00672074, NCT01280344) reached Phase 2; the pivotal Phase 2 trial published by Beck et al. (2014: 25.3 vs 32.6 h, P=0.15) failed its primary endpoint and the programme was discontinued for lack of efficacy. Some secondary sources reference Phase 3 codes IPA-AS-301 / IPA-AS-302; these were NOT verifiable against the ClinicalTrials.gov v2 API or Helsinn press archives — ipamorelin did NOT reach Phase 3. Ipamorelin is NOT approved by the FDA, EMA, or any other regulator; in sport it is named explicitly on the WADA Prohibited List 2026 under section S2.2.4 (growth-hormone secretagogues and their mimetics).

Identity & Chemistry

Two-dimensional skeletal structural formula of ipamorelin, a synthetic pentapeptide showing the C-terminal lysinamide, D-phenylalanine and D-2-naphthylalanine residues, the central histidine imidazole, and the N-terminal α-aminoisobutyric acid (Aib) group.
Image credit: Edgar181, via Wikimedia Commons · Public Domain
Amino Acid Sequence
H-Aib-His-D-2-Nal-D-Phe-Lys-NH₂ — five residues, C-terminal lysinamide. Position 1 is α-aminoisobutyric acid (Aib, non-proteinogenic); position 3 is D-2-naphthylalanine; position 4 is D-phenylalanine. The free base is C₃₈H₄₉N₉O₅ (711.86 g·mol⁻¹, CAS 170851-70-4); most research-grade material is supplied as the acetate salt — vendor catalog molecular weights for the acetate vary slightly with stoichiometry of bound acetate counter-ion.
Molecular Formula
C₃₈H₄₉N₉O₅ (free base; PubChem CID 9831659)
Molecular Weight
711.86 g·mol⁻¹ (free base; the acetate salt commonly supplied for research adds ~60 Da per acetate counter-ion)
CAS Number
170851-70-4 (free base)
PubChem CID
9831659
IUPAC Name
(2S)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2S)-2-[(2-amino-2-methylpropanoyl)amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-3-naphthalen-2-ylpropanoyl]amino]-3-phenylpropanoyl]amino]hexanamide. Ipamorelin has no canonical DrugBank approved-drug monograph as of May 2026; UNII Y9M3S784Z6.
Solubility
Water-soluble as the acetate salt at the concentrations used for subcutaneous or intravenous research administration. Quantitative aqueous solubility (mg/mL) is not publicly disclosed by Novo Nordisk or downstream sponsors.
Storage
Lyophilised peptide: store at −20 °C, sealed and protected from light. Reconstituted aliquots: 2–8 °C for short-term (days) use; −20 °C for longer-term storage. Avoid repeated freeze-thaw cycles.

Mechanism of Action

Ipamorelin is a synthetic pentapeptide and ghrelin mimetic that selectively activates the growth-hormone-secretagogue receptor type 1a (GHSR-1a) on pituitary somatotrophs, evoking a pulsatile release of endogenous GH — without measurable elevation of ACTH, cortisol, prolactin, FSH, LH, or TSH at GH-effective doses.

Ipamorelin (NNC 26-0161) was synthesised by the Novo Nordisk peptide-discovery programme in the late 1990s by structural variation of GHRP-1, with the explicit goal of dissociating GH-releasing activity from the cortisol- and prolactin-stimulating side effects characteristic of earlier GHRPs (Raun 1998). Mechanistically it acts upstream of the somatotroph at GHSR-1a, the same receptor as endogenous ghrelin; binding triggers the canonical Gq/PLCβ pathway, mobilising intracellular Ca²⁺ and producing immediate GH exocytosis, while a parallel hypothalamic effect attenuates somatostatin tone and synergises with endogenous GHRH at the GHRHR. In healthy male volunteers, single 15-minute IV infusions across 4.21–140.45 nmol/kg produced a single GH peak ~40 minutes after dosing with PK described by a half-life of approximately 2 hours, clearance of 0.078 L/h/kg, and dose-proportional exposure (Gobburu 1999). Importantly, ipamorelin's GHSR-1a-mediated mechanism is mechanistically distinct from the GHRHR class (sermorelin, tesamorelin, CJC-1295), and its selectivity profile is also distinct within the GHRP class: hexarelin engages off-target CD36 with cardiac effects, GHRP-6 stimulates cortisol and prolactin, and GHRP-2 raises ACTH and cortisol — ipamorelin remains, more than 25 years after its discovery, the cleanest published GH/cortisol/prolactin/ACTH selectivity within the GHRP-class chemistry.

Molecular Targets

  • GHSR-1a (growth-hormone-secretagogue receptor type 1a; UniProt Q92847) — the ghrelin receptor; class A G-protein-coupled receptor expressed on pituitary somatotrophs, hypothalamic arcuate-nucleus neurons, vagal afferents, and gut enteric neurons
  • No meaningful agonism at the GHRH receptor (GHRHR) — mechanistically distinct from sermorelin, tesamorelin, and CJC-1295
  • No measurable HPA-axis activation (ACTH/cortisol) and no elevation of prolactin, FSH, LH, or TSH at GH-effective doses — the defining selectivity of ipamorelin within the GHRP class

Signaling Pathways

  • GHSR-1a → Gαq/11 → phospholipase Cβ → IP₃ + DAG → ↑ intracellular Ca²⁺ and PKC activation → Ca²⁺-dependent exocytotic release of GH from somatotroph secretory granules
  • A secondary Gαs/cAMP arm contributes to GH exocytosis
  • Hypothalamic component: suppression of somatostatin tone and synergy with endogenous GHRH at GHRHR
  • Systemic outcome: pulsatile rise in plasma GH within minutes of administration, with downstream hepatic IGF-1 generation; endogenous somatostatin and IGF-1 negative feedback are preserved

Research Applications

Ipamorelin has been studied in a foundational pharmacology paper (Raun 1998), a Phase 1 PK/PD study in healthy men (Gobburu 1999), two preclinical bone-growth studies (Johansen 1999; Andersen 2001), and a two-trial Phase 2 programme in post-operative ileus (Beck 2014; NCT00672074, NCT01280344). The evidence base is concentrated in the Novo Nordisk and Helsinn programmes. All findings are reported as investigational and for research use only.

Discovery and selective GH release in animals and humans (Raun 1998)

preclinical

Studies report that ipamorelin stimulated GH release from rat anterior pituitary cells with a potency comparable to GHRP-6 (EC₅₀ in the low-nanomolar range) and produced GH peaks of similar magnitude to GHRP-6 in conscious swine. Selectivity was the headline result: at doses up to 200-fold the GH-effective dose, ipamorelin did not raise plasma ACTH or cortisol above the levels evoked by GHRH and did not affect FSH, LH, prolactin, or TSH — whereas GHRP-6 and GHRP-2 in the same paradigm raised ACTH and cortisol.

— Raun et al., Eur J Endocrinol 1998;139(5):552–561 (PMID 9849822)

Pharmacokinetics / pharmacodynamics in healthy volunteers (Gobburu 1999)

Phase I

Studies report, in an open-label dose-escalation study in healthy male volunteers (eight subjects per dose at 4.21, 14.02, 42.13, 84.27, and 140.45 nmol/kg administered as 15-minute IV infusions), a half-life of ~2 hours, clearance of 0.078 L/h/kg, volume of distribution of 0.22 L/kg, and dose-proportional exposure. Pharmacodynamically, a single GH peak appeared at a median 0.67 h after dosing; SC₅₀ ~214 nmol/L; maximum GH production rate ~694 mIU/L/h.

— Gobburu et al., Pharm Res 1999;16(9):1412–1416 (PMID 10496658)

Longitudinal bone growth in adult rats (Johansen 1999)

preclinical

Studies report, in a controlled preclinical study in adult female rats (subcutaneous ipamorelin 0 / 18 / 90 / 450 µg three times daily for 15 days; tetracycline-labelling assay), a dose-dependent increase in longitudinal growth rate from 42 µm/day in vehicle controls to 44, 50, and 52 µm/day in the three ipamorelin dose groups (P < 0.0001), accompanied by a pronounced dose-dependent gain in body weight. Total IGF-1, IGF-binding proteins, pituitary GH content, and bone-resorption markers were unchanged.

— Johansen et al., Growth Horm IGF Res 1999;9(2):106–113 (PMID 10373343)

Counteracting glucocorticoid-induced bone loss (Andersen 2001)

preclinical

Studies report, in a controlled preclinical study in 8-month-old female Wistar rats (3-month exposure; methylprednisolone 9 mg/kg/day SC ± ipamorelin 100 µg/kg three times daily SC vs vehicle), a roughly four-fold higher periosteal bone-formation rate in animals receiving glucocorticoid + ipamorelin compared with glucocorticoid alone; maximum tetanic tension in calf muscles was significantly improved with combined treatment.

— Andersen et al., Growth Horm IGF Res 2001;11(5):266–272 (PMID 11735244)

Post-operative ileus — Phase 2 proof-of-concept (Beck 2014; NCT00672074)

Phase II

Multicenter, double-blind, randomised, placebo-controlled Phase 2 proof-of-concept trial in patients undergoing bowel resection with primary anastomosis (n=117 enrolled, 114 evaluable; Helsinn ST-IPAM-201). IV ipamorelin 0.03 mg/kg twice daily vs placebo from postoperative day 1 to day 7 or hospital discharge. Primary endpoint (median time from first dose to tolerance of standardised solid meal): 25.3 h ipamorelin vs 32.6 h placebo, P=0.15 — the trial did not meet its primary endpoint. Treatment-emergent adverse events: 87.5% (ipamorelin) vs 94.8% (placebo) — comparable safety.

— Beck et al., Int J Colorectal Dis 2014;29(12):1527–1534 (PMID 25331030); NCT00672074

Post-operative gastrointestinal recovery — Phase 2 dose-finding study (NCT01280344)

Phase II

Multicenter, double-blind, placebo-controlled Phase 2 dose-finding study (Helsinn HT-IPAM-202; actual enrolment n=320). Three IV ipamorelin regimens (0.03 mg/kg BID, 0.06 mg/kg BID, 0.06 mg/kg TID) vs saline placebo, evaluated within 10 days postoperatively. Trial completed May 2014 (primary completion June 2013). No primary-outcome results have been posted to ClinicalTrials.gov (hasResults: false); the broader Helsinn ipamorelin POI programme was discontinued after this study for lack of efficacy.

— ClinicalTrials.gov NCT01280344 (verified vs v2 API on 2026-05-01)

Clinical Status

Regulatory Status
NOT approved by the FDA, EMA, Health Canada, or any other major regulatory agency. Ipamorelin was never submitted for FDA approval and has no ATC code. Highest verified clinical phase: Phase 2 (Helsinn-sponsored post-operative ileus / gastrointestinal-recovery programme; NCT00672074 and NCT01280344, both verified vs ClinicalTrials.gov v2 API on 2026-05-01). The Phase 2 programme failed its primary endpoint (Beck 2014: 25.3 vs 32.6 h, P=0.15) and was subsequently discontinued for lack of efficacy. Some secondary sources reference Phase 3 codes IPA-AS-301 and IPA-AS-302; these were NOT verifiable against the ClinicalTrials.gov v2 API or Helsinn press archives at the time of this entry — the page describes the programme correctly as "Phase 2 program failed to meet its primary endpoint and was discontinued," not as Phase 3. Sport: prohibited under the WADA Prohibited List 2026, named explicitly under section S2.2.4 (growth-hormone secretagogues and their mimetics) — both in- and out-of-competition. Material from research-chemical suppliers is not regulatory approval and not a Triscience endorsement.
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Highest Trial Phase
Phase II (Helsinn POI programme; primary endpoint not met; programme discontinued); other data Phase I (healthy adults)
Sponsor
Originator: Novo Nordisk A/S (Denmark; internal discovery-programme code NNC 26-0161, late 1990s). Phase 2 sponsor: Helsinn Therapeutics (US), Inc. — post-operative ileus / gastrointestinal-recovery programme, subsequently discontinued.

Key Clinical Trials

  • A Phase II, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Evaluate the Safety and Efficacy of Ipamorelin Compared to Placebo for the Management of Post-Operative Ileus (Helsinn ST-IPAM-201; n=117; primary endpoint not met — 25.3 vs 32.6 h, P=0.15; verified vs ClinicalTrials.gov v2 API on 2026-05-01).
    Phase 2
    NCT00672074
  • Phase II Double-Blind Placebo-Controlled Dose Finding Study to Evaluate Safety/Efficacy of Ipamorelin Compared to Placebo for Recovery of Gastrointestinal Function in Patients Following Small or Large Bowel Resection With Primary Anastomosis (Helsinn HT-IPAM-202; n=320; completed May 2014; no primary-outcome results posted; programme discontinued for lack of efficacy; verified vs ClinicalTrials.gov v2 API on 2026-05-01).
    Phase 2
    NCT01280344

Safety Profile

Observed in research settings

In the published Phase 2 trials and earlier human PK/PD work, ipamorelin was reported as well tolerated in research settings, with adverse-event rates comparable to placebo and no serious safety signal that would have terminated the programme (the Phase 2 programme ended for lack of efficacy, not safety). The principal pharmacological signature — selective GH release without ACTH/cortisol/prolactin elevation at GH-effective doses — has been replicated across animal and early human studies (Raun 1998; Gobburu 1999; Beck 2014).

Adverse Events Reported in Studies

  • Treatment-emergent adverse events comparable between arms overall (Beck 2014: 87.5% ipamorelin vs 94.8% placebo)
  • Postoperative pain, nausea, constipation, headache, and abdominal symptoms (not differentiable from placebo in Beck 2014)
  • Transient elevation of GH and downstream IGF-1 — consistent with the intended mechanism
  • Injection-site reactions (class-typical for IV/SC peptide preparations)

Serious Adverse Events

  • No dose-limiting toxicity in published human studies up to 140.45 nmol/kg single IV dose (Gobburu 1999) or 0.03–0.06 mg/kg BID/TID multiple-dose IV regimens (Beck 2014; NCT01280344)
  • Long-term (multi-year) safety data in humans are absent because development was discontinued at Phase 2 — chronic-use claims by wellness or performance-enhancement vendors are not supported by published evidence
  • Theoretical class-related concerns (transient hyperglycaemia / impaired glucose tolerance, fluid retention, paraesthesia, theoretical neoplasm-promotion in pre-existing malignancy) have not been systematically characterised for ipamorelin
  • Anti-doping liability: ipamorelin is named explicitly on the WADA Prohibited List 2026 under S2.2.4 (growth-hormone secretagogues) — both in- and out-of-competition

References

  1. Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol 1998;139(5):552–561. 1998 .

    DOI: 10.1530/eje.0.1390552 PMID: 9849822 View Source

  2. Gobburu JV, Agersø H, Jusko WJ, Ynddal L Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res 1999;16(9):1412–1416. 1999 .

    DOI: 10.1023/A:1018955126402 PMID: 10496658 View Source

  3. Johansen PB, Nowak J, Skjaerbaek C, Flyvbjerg A, Andreassen TT, Wilken M, Ørskov H Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res 1999;9(2):106–113. 1999 .

    DOI: 10.1054/ghir.1999.9998 PMID: 10373343 View Source

  4. Andersen NB, Malmlöf K, Johansen PB, Andreassen TT, Ørtoft G, Oxlund H The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Horm IGF Res 2001;11(5):266–272. 2001 .

    DOI: 10.1054/ghir.2001.0239 PMID: 11735244 View Source

  5. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. Int J Colorectal Dis 2014;29(12):1527–1534. 2014 .

    DOI: 10.1007/s00384-014-2030-8 PMID: 25331030 View Source

  6. Helsinn Therapeutics (US) / ClinicalTrials.gov Safety and Efficacy of Ipamorelin Compared to Placebo for the Management of Post-Operative Ileus (NCT00672074; ST-IPAM-201). Phase 2; n=117; completed December 2009; verified vs ClinicalTrials.gov v2 API on 2026-05-01. ClinicalTrials.gov registry record. 2009 .

    View Source

  7. Helsinn Therapeutics (US) / ClinicalTrials.gov Phase II Double-Blind Placebo-Controlled Dose Finding Study to Evaluate Safety/Efficacy of Ipamorelin (NCT01280344; HT-IPAM-202). Phase 2; n=320; completed May 2014; no primary-outcome results posted; verified vs ClinicalTrials.gov v2 API on 2026-05-01. ClinicalTrials.gov registry record. 2014 .

    View Source

  8. PubChem Ipamorelin, CID 9831659 — molecular formula C₃₈H₄₉N₉O₅; average mass 711.9; InChI Key NEHWBYHLYZGBNO-BVEPWEIPSA-N. National Library of Medicine, PubChem record. 2025 .

    View Source

  9. World Anti-Doping Agency The 2026 Prohibited List — International Standard. Section S2.2.4 (growth-hormone secretagogues and their mimetics) names ipamorelin explicitly alongside anamorelin, capromorelin, ibutamoren (MK-677), lenomorelin (ghrelin), macimorelin, and tabimorelin. WADA, effective 1 January 2026. 2026 .

    View Source

Frequently Asked Questions

What is ipamorelin?
Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) discovered by Novo Nordisk in the late 1990s under the development code NNC 26-0161. It binds the growth-hormone-secretagogue receptor 1a (GHSR-1a, the ghrelin receptor) on pituitary somatotrophs, evoking a discrete pulse of endogenous growth hormone. Its defining property is selective GH release without measurable elevation of ACTH, cortisol, prolactin, FSH, LH, or TSH — historically the cleanest selectivity of any GHRP-class peptide (Raun 1998).
How does ipamorelin differ from sermorelin or tesamorelin?
Sermorelin (GHRH 1-29) and tesamorelin (acylated GHRH 1-44) act at the GHRH receptor (GHRHR) on somatotrophs. Ipamorelin acts at a different receptor — GHSR-1a, the ghrelin receptor — and is mechanistically a ghrelin mimetic. Both classes ultimately raise endogenous GH and IGF-1, but their molecular targets, downstream signalling (Gαs/cAMP for GHRHR vs Gαq/Ca²⁺ for GHSR-1a), and pharmacological side-effect profiles differ. Ipamorelin is unusual within the GHRP/GHS class for not raising cortisol or prolactin.
How does ipamorelin differ from GHRP-6, GHRP-2, or hexarelin?
All four are GHSR-1a agonists, but at GH-effective doses GHRP-6 and GHRP-2 also raise ACTH, cortisol, and prolactin, and hexarelin engages the off-target CD36 receptor with cardiac effects. Ipamorelin's reported selectivity for GH without those off-targets — established by Raun et al. (1998) — is the single feature most cited as distinguishing it within the GHRP class.
Is ipamorelin approved by the FDA or EMA?
No. Ipamorelin has never been approved by the FDA, EMA, or any other regulator. The most advanced clinical development was a Phase 2 programme by Helsinn Therapeutics for post-operative ileus / gastrointestinal recovery after bowel resection (NCT00672074 and NCT01280344). The pivotal Phase 2 trial published by Beck et al. (2014, Int J Colorectal Dis.) failed to meet its primary endpoint (median time to first tolerated meal 25.3 h ipamorelin vs 32.6 h placebo, P=0.15), and the programme was discontinued for lack of efficacy. Ipamorelin did NOT reach Phase 3 — codes IPA-AS-301 / IPA-AS-302 cited in some secondary commentary could not be verified in any public source.
Is ipamorelin permitted in sport?
No. Ipamorelin is named explicitly on the World Anti-Doping Agency (WADA) Prohibited List 2026 under section S2.2.4 ("growth-hormone secretagogues (GHS) and their mimetics") — prohibited at all times, both in- and out-of-competition. Other GHS-class compounds named alongside it include anamorelin, capromorelin, ibutamoren (MK-677), lenomorelin (ghrelin), macimorelin, and tabimorelin.
What is the molecular structure of ipamorelin?
Ipamorelin is a five-residue peptide with the sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (C-terminal lysinamide; α-aminoisobutyric acid at position 1, D-2-naphthylalanine at position 3, D-phenylalanine at position 4). Molecular formula C₃₈H₄₉N₉O₅, average mass 711.86 g·mol⁻¹, CAS 170851-70-4 (free base), PubChem CID 9831659, InChI Key NEHWBYHLYZGBNO-BVEPWEIPSA-N. The free base is the chemically defined active species; most research-grade material is supplied as the acetate salt.

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CJC-1295

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GHRH(1-29) Analogue with Drug Affinity Complex (Growth-Hormone Secretagogue, GRF Class)

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GHRH(1-44) Receptor Agonist (Growth-Hormone Secretagogue, GRF Class)

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