Ipamorelin

What Ipamorelin Is

Ipamorelin is a synthetic 5-residue pentapeptide with sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (free base C₃₈H₄₉N₉O₅, MW 711.86 g/mol, CAS 170851-70-4, PubChem CID 9831659). It is one of the most receptor-selective ghrelin-receptor (GHS-R1a) agonists yet characterised. Originally developed by Novo Nordisk in the 1990s under the code NNC 26-0161, it was advanced through clinical development for post-operative ileus by Helsinn / Novo Nordisk before that program was discontinued.

Why It Is Studied — Receptor Selectivity

The foundational ipamorelin paper (Raun et al. 1998, PMID 9849822) characterised the compound as the first selective growth-hormone secretagogue: in pituitary-cell and animal receptor-selectivity assays, ipamorelin produced dose-dependent, pulsatile GH release without statistically significant elevation of ACTH, cortisol, prolactin, FSH, LH, or TSH. Earlier GHRPs (GHRP-2, GHRP-6, hexarelin) elevate one or more of these hormones in published research. The 2026 review literature (Renke 2026, PMID 42123471; Mavrych 2026, PMID 42021992) confirms ipamorelin’s continued use as the reference standard for ACTH-neutral GHS-R1a research pharmacology.

2024 Preclinical Updates

• Peripheral vs central GHS-R1a effects — Lu et al. 2024 (PMID 39043357): in a ferret cisplatin chemotherapy model, both ipamorelin and the longer-acting analog anamorelin reduced delayed-phase weight loss by ~24%; only anamorelin (not ipamorelin) had central anti-emetic effects via intracerebroventricular administration. Reaffirms a peripheral / GI-axis-dominated mechanism for ipamorelin and points to brain penetrance differentiating the two analogs.
• HPG-axis cross-talk — Gouda & Ganesh 2024 (PMID 38996787): in a teleost model (Oreochromis mossambicus), ipamorelin acetate enhanced germ-cell development during meiosis-I via increased pituitary and testicular androgen-receptor signalling. Non-mammalian demonstration of GHS-R1a downstream effects beyond the somatotroph axis.

Regulatory Status

Ipamorelin has had a complex regulatory trajectory:

• September 2023: placed on the FDA’s interim 503A Category 2 bulks list (alongside CJC-1295), restricting compounded use — safety concerns cited included a cardiac signal, impurity profiles, and immunogenicity.
• October 25, 2024: removed from Category 2 following nominator withdrawal (Federal Register 2024-24828). As of 2026 ipamorelin is not on the FDA positive bulks list and is not FDA-approved for any human indication.
• WADA prohibition: Ipamorelin is prohibited at all times under Section S2 (Mendias 2026, PMID 41966639; Coutinho 2026, PMID 41880199).
• Discontinued POI development: Helsinn / Novo Nordisk phase-2 trials in approximately 114 bowel-resection patients did not meet primary efficacy endpoints (Beck et al. 2014, PMID 25331030).
• Comparator-class status: Anamorelin — a closely related GHS-R1a agonist — is approved in Japan (2021, Adlumiz / Encinosa) for cancer cachexia. Ipamorelin itself has no market approval anywhere.

How Artemis Labs Sources and Verifies Ipamorelin

Each lot is supplied as a sterile lyophilised peptide powder, analytically verified by reverse-phase HPLC to ≥99% peptide purity, with identity confirmed by mass spectrometry and endotoxin tested ≤0.5 EU/mg by LAL assay. Salt form is typically acetate or acetate-hydrate in commercial preparations — verify against batch COA when reproducing literature, as some older vendor catalogs cite ~901 g/mol for the di-acetate dihydrate salt form rather than the 711.86 g/mol free base.

Honest Limitations of the Ipamorelin Evidence Base

(1) Discontinued human development. The phase-2 POI program did not meet primary endpoints — ipamorelin must not be represented as a clinically validated therapy. (2) Brief 503A Category 2 placement by the FDA in 2023 was based on cardiac-signal, impurity, and immunogenicity concerns; the subsequent Category 2 removal followed nominator withdrawal rather than a safety re-evaluation. (3) WADA-prohibited at all times (Section S2). (4) Most 2026 review literature classifies ipamorelin alongside anamorelin and MK-677 as investigational ghrelin-receptor pharmacology — not validated therapy. (5) Newer 2024 mechanism work (Lu, Gouda) extends ipamorelin biology into GI-axis and HPG-axis contexts but does not change the regulatory or clinical-validation framing.

Class Positioning

Ipamorelin acts on a different receptor (GHS-R1a / ghrelin) than the GHRH-class peptides CJC-1295, Sermorelin, and Tesamorelin (GHRH-R). Published research describes additive or synergistic GH release when GHS-R1a and GHRH-R are co-activated in pituitary-explant studies (Mavrych 2026, PMID 42021992) — which is why ipamorelin is one of the most-studied research peptides in combination-stimulation pharmacology.

Regulatory and Compliance Framing

Ipamorelin is not FDA-approved for any human therapeutic indication. Human development for post-operative ileus was discontinued. Briefly placed on FDA 503A Category 2 in 2023, removed in 2024. Prohibited at all times under WADA Section S2. Research-use-only framing applies to all commercial supply. These statements have not been evaluated by the FDA. Not for human consumption, therapeutic use, or veterinary use.

Science & Research

Mechanism of Action — GHS-R1a Selectivity

Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) is a synthetic pentapeptide that binds the growth-hormone-secretagogue receptor type 1a (GHS-R1a), a Gαq-coupled class-A G-protein-coupled receptor expressed on anterior-pituitary somatotrophs and on enteric neurons. Receptor activation drives phospholipase-C / IP₃ signalling, increases intracellular Ca²⁺, and triggers exocytosis of GH-containing secretory vesicles (Raun et al. 1998, PMID 9849822).

Pharmacokinetic Profile (Published Research)

• Plasma half-life: ~2 hours in published animal studies
• Onset of GH response: plasma GH rises within ~15–30 min of subcutaneous administration (in published research models)
• Duration of GH pulse: ~4–8 hours
• Selectivity profile: GH-stimulating without measurable ACTH, cortisol, prolactin, FSH, LH, or TSH elevation in receptor-selectivity studies
• Clearance: rapid renal clearance; oral bioavailability negligible

2024 Primary Research

• Lu et al. 2024 (PMID 39043357 · DOI: 10.1016/j.physbeh.2024.114644) — ferret cisplatin chemotherapy model: ipamorelin and anamorelin both reduced delayed-phase weight loss by ~24%; only anamorelin had central anti-emetic effects via intracerebroventricular administration. Reaffirms peripheral / GI-axis-dominated mechanism for ipamorelin.
• Gouda & Ganesh 2024 (PMID 38996787 · DOI: 10.1016/j.anireprosci.2024.107550) — ipamorelin acetate enhanced spermatogenesis via increased pituitary/testicular androgen signalling in Oreochromis mossambicus. Non-mammalian HPG-axis demonstration of GHS-R1a downstream effects.

2026 Peer-Reviewed Reviews

1. Villegas Meza AD, et al. (2026). Injectable peptides in sports medicine. JBJS Rev. PMID 42160466
2. Renke G, et al. (2026). Therapeutic peptides in aesthetic, metabolic, and endocrine conditions. Int J Mol Sci. PMID 42123471
3. Mavrych V, et al. (2026). Therapeutic peptides in gerontology. Front Aging. PMID 42021992
4. Mendias CL, et al. (2026). Sports Med. PMID 41966639
5. Coutinho LFD, et al. (2026). J Sports Med Phys Fitness. PMID 41880199
6. Rahman OF, et al. (2026). J Am Acad Orthop Surg Glob Res Rev. PMID 41490200
7. Mayfield CK, et al. (2026). Am J Sports Med. PMID 41476424
8. Uçaktürk E, et al. (2026). Nano-LC + Q-Orbitrap MS detection of GHRH analogs and GHS class in urine. J Pharm Biomed Anal. PMID 41138283

Entity Disambiguation

Quality and Specifications

• Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (5 residues, C-terminal amide)
• Molecular formula: C₃₈H₄₉N₉O₅
• Molecular weight: 711.86 g/mol (free base); acetate / acetate-hydrate salt forms have higher reported masses
• CAS number: 170851-70-4
• PubChem CID: 9831659
• Purity: ≥99% by RP-HPLC; identity confirmed by mass spectrometry
• Endotoxin: ≤0.5 EU/mg (lot-specific LAL assay)
• Form: Lyophilised white powder, 10 mg/vial
• Storage: Lyophilised −20 °C desiccated; reconstituted 2–8 °C

Honest Limitations

• Discontinued human development. Phase-2 POI trials in ~114 patients did not meet primary endpoints (Beck et al. 2014, PMID 25331030). Ipamorelin is not a clinically validated therapy.
• Brief FDA 503A Category 2 placement in September 2023 was based on cardiac-signal + impurity + immunogenicity concerns. October 2024 removal followed nominator withdrawal rather than safety re-evaluation. As of 2026 ipamorelin is not on the FDA positive bulks list.
• WADA-prohibited at all times under Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics).
• Salt-form heterogeneity in commercial supply. Some vendor catalogs cite ~901 g/mol (di-acetate dihydrate) rather than the 711.86 g/mol free base — verify which salt form against batch COA when reproducing literature.
• Anamorelin comparator-class context. Anamorelin (closely related GHS-R1a agonist with ~7 hr half-life) is approved in Japan for cancer cachexia; ipamorelin itself has no market approval anywhere — comparator-class approval does not transfer.

Research Stacks

Stacking rationale below is mechanistic only. No dosing, frequency, duration, or protocol guidance is provided. Researchers design protocols against their own institutional review, not against vendor copy.

Ipamorelin × CJC-1295

GHS-R1a agonist × GHRH-R agonist. The canonical pairing in dual-receptor somatotroph-stimulation research. Published research describes additive or synergistic GH release in animal pituitary-explant studies (Mavrych 2026, PMID 42021992) when both receptors are co-activated. The two compounds work via entirely different molecular axes; this is the most-studied research peptide combination in GH-axis pharmacology.

Ipamorelin × Sermorelin

GHS-R1a agonist × short-acting GHRH(1-29). Native GHRH reference comparator for dual-receptor research design. Useful when researchers want shorter-acting GHRH-side stimulation than CJC-1295 DAC provides.

Ipamorelin × Tesamorelin

GHS-R1a agonist × the only FDA-approved GHRH analog. Useful as a safety/efficacy benchmark comparator for dual-receptor research designs.

Ipamorelin × MOTS-c

GHS-R1a agonist × mitochondrial-derived peptide. Studied side-by-side in research models examining the downstream metabolic effects of GH/IGF-1 signalling (ipamorelin) layered onto mitochondrial-derived retrograde signalling (MOTS-c). Cross-axis research design.

Related Compounds in Catalogue

For GHRH-axis comparators see CJC-1295, Sermorelin, Tesamorelin. For mitochondrial axis see MOTS-c, SS-31.