CJC-1295 vs Ipamorelin: GHRH Analog vs Ghrelin Mimetic

Research-use-only context. This article summarizes published third-party scientific literature and laboratory practice. It is not medical advice, not a therapeutic or performance claim, and not a usage guide. US Prime Peptides products are supplied strictly for in vitro laboratory research and are not for human or veterinary use.

CJC-1295 and ipamorelin are sold together so often that many buyers assume they are variations on one molecule. They are not. This article compares the two at the level of sequence, mass, receptor class, chemical modifications, development history, and what the certificate for each (or for the blend) must show.

The short answer: two receptors, two unrelated peptides

CJC-1295 is a modified fragment of growth hormone-releasing hormone (GHRH) that binds the GHRH receptor, a class B G-protein-coupled receptor cloned from rat pituitary by Mayo in 1992. Ipamorelin is a five-residue synthetic peptide with no sequence relationship to GHRH that binds the growth hormone secretagogue receptor (GHS-R1a), a class A G-protein-coupled receptor cloned by Howard and colleagues in 1996 and later identified as the ghrelin receptor. The two receptors sit on the same pituitary somatotroph but couple through different G proteins: GHRH-R through G_s and cyclic AMP, GHS-R1a mainly through G_q and intracellular calcium.

CJC-1295 is a 29- or 30-residue peptide of roughly 3.4 to 3.6 kDa depending on whether it carries the albumin-binding tail. Ipamorelin is about 712 Da. Neither is an approved drug anywhere. The single-compound articles on CJC-1295 and ipamorelin cover each in depth; the article on GPCRs explains the receptor families involved.

CJC-1295: a four-substitution GRF(1-29) with or without an albumin tail

CJC-1295 starts from the first 29 residues of human GHRH, the same fragment sold as sermorelin, and makes four substitutions: D-Ala at position 2, Gln at position 8, Ala at position 15, and Leu at position 27. Each has a chemical rationale. A 1991 Hormone and Metabolic Research paper by Su and colleagues showed that native GRF(1-29)-NH₂ has a half-life of about 13 minutes in porcine plasma and is cleaved almost entirely to GRF(3-29) by dipeptidyl peptidase IV at the Ala2-Asp3 bond; a D-amino acid at position 2 blocks that cut. Gln8 replaces an asparagine prone to deamidation, Ala15 replaces a glycine (the same paper reported that Ala15 alone modestly slowed plasma degradation), and Leu27 replaces a methionine that oxidizes during storage.

The version known as "CJC-1295 with DAC" adds a thirtieth residue, a lysine carrying an N-epsilon-3-maleimidopropionamide group. The 2005 Endocrinology paper by Jetté and colleagues that named CJC-1295 describes this "Drug Affinity Complex" as a maleimide that forms a covalent thioether bond with the single free thiol, Cys34, of serum albumin. In their rat work the conjugated peptide was still detectable in plasma beyond 72 hours, and a 2006 Journal of Clinical Endocrinology and Metabolism paper by Ionescu and Frohman reported an eight-day half-life in healthy men with growth hormone pulsatility preserved. The version sold as "Mod GRF(1-29)" or "CJC-1295 without DAC" is the same four-substitution peptide with no maleimide lysine, so it has no albumin-binding mechanism and a far shorter plasma residence.

On a certificate the two are different molecules: the 29-residue peptide has an average mass near 3,368 Da, the DAC form near 3,648 Da. A vendor listing must say which one it is, and the mass-spectrometry identity line must match.

Ipamorelin: a pentapeptide ghrelin mimetic

Ipamorelin is Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (molecular formula C₃₈H₄₉N₉O₅, average mass about 711.9 Da). Aib is alpha-aminoisobutyric acid, a non-proteinogenic residue; D-2-Nal is D-3-(2-naphthyl)alanine. The peptide was identified at Novo Nordisk, and the 1998 European Journal of Endocrinology paper by Raun and colleagues that introduced it describes it as emerging from a series of compounds that lacked the central Ala-Trp dipeptide of GHRP-1. In rat primary pituitary cells it released growth hormone with an EC₅₀ of 1.3 nM and an efficacy comparable to GHRP-6, and the authors reported that, unlike GHRP-2 and GHRP-6, it did not release ACTH or cortisol at growth hormone-releasing concentrations in swine, which is the basis for the word "selective" in the paper's title.

A 1998 Xenobiotica paper by Johansen and colleagues compared the pharmacokinetics of ipamorelin with GHRP-2 and GHRP-6 in rats and found that ipamorelin had a systemic plasma clearance about five-fold lower than GHRP-6 and was excreted mainly in urine rather than bile. Novo Nordisk later used ipamorelin as the lead for the orally active non-peptide NN703. A 2009 J Pharmacol Exp Ther paper by Venkova and colleagues studied ipamorelin in a rat model of postoperative ileus.

Side-by-side comparison

In short, a blend of these two is a 3.4 kDa peptide plus a 0.7 kDa peptide acting on different receptors, not two strengths of one thing.

Two receptors on one cell: why the pair is studied together

The reason the two are paired in research catalogs is a receptor-level observation that predates both compounds. A 1997 Life Sciences paper by Cheng and colleagues showed in rat primary pituitary cells that growth hormone-releasing peptides acting at the secretagogue receptor and GRF acting at the GHRH receptor release growth hormone synergistically, that GHRPs desensitize cells to each other but not to GRF, and that a GRF antagonist does not block the GHRP response. Bowers' 2012 historical review in Methods in Enzymology traces the GHRP-plus-GHRH synergy finding back to the 1980s and credits it with motivating the search that ended in the cloning of GHS-R1a and the discovery of ghrelin.

That is the basis for the pairing: two independent inputs to one cell. The published synergy data come from rat pituitary cells and from GHRP-2, GHRP-6 and native GRF, not from a defined CJC-1295-plus-ipamorelin mixture. No peer-reviewed study tests the commercial blend as such.

What each certificate line must show

For a single-compound vial, the identity line should report an observed mass that matches the declared form of CJC-1295 (with or without DAC) or the 711.9 Da ipamorelin mass. For a blend, the certificate must resolve both. Because the two differ nearly five-fold in mass, they are trivially distinguished by mass spectrometry and elute at very different retention times on reverse-phase HPLC, so per-component purity is straightforward to report. What mass spectrometry cannot do is confirm the D-configuration at Ala2 of CJC-1295 or at the 2-Nal and Phe positions of ipamorelin; a D-residue has the same mass as its L-enantiomer. Only a chiral amino acid analysis can verify that, and most research certificates omit it. The article on reading a blend certificate covers the co-elution and ratio questions in detail.

US Prime Peptides lists Ipamorelin 10 mg as a single-compound vial and CJC-1295/Ipamorelin 5 mg + 5 mg as a blend, each with a lot-matched certificate reporting identity by mass spectrometry, HPLC purity, net peptide content, endotoxin, sterility and heavy metals, posted before purchase. The CJC-1295 form in the blend is stated on the product page and should be read against the observed mass on the certificate.

Regulatory status and development history

Neither compound is an approved drug in the United States or elsewhere. CJC-1295 was developed by ConjuChem in Montreal; the 2006 American Journal of Physiology paper by Alba and colleagues used it in GHRH-knockout mice, and the Ionescu and Frohman human study and a 2009 Growth Hormone and IGF Research serum-proteomics study by Sackmann-Sala and colleagues are the main published human data. The program did not proceed to approval. Ipamorelin's Novo Nordisk program ended with the pivot to NN703, and Helsinn's later program did not reach approval either. A 2019 Drug Testing and Analysis paper by Timms and colleagues describes an LC-MS/MS method for confirming CJC-1295 in equine plasma and notes that the albumin-conjugated form is difficult to detect by mass spectrometry because of its low abundance and high molecular weight, which is relevant to any laboratory planning to quantify it. Both compounds appear in the growth-hormone-releasing categories of the WADA Prohibited List. A research vial of either is supplied only for in vitro work.

Frequently Asked Questions

Is CJC-1295 the same as ipamorelin?

No. CJC-1295 is a modified 29-residue fragment of GHRH that binds the GHRH receptor; ipamorelin is a synthetic 5-residue peptide that binds the ghrelin receptor GHS-R1a. They differ nearly five-fold in mass and share no sequence.

What is the difference between CJC-1295 with DAC and without DAC?

The DAC form carries an extra lysine with a maleimide group that bonds covalently to Cys34 of serum albumin; the non-DAC form (often called Mod GRF 1-29) has the same four amino-acid substitutions but no maleimide lysine. The masses differ by about 280 Da, so the certificate's identity line tells you which one is in the vial.

Why are CJC-1295 and ipamorelin sold as a blend?

Because they act on two different receptors on the same pituitary cell, and rat pituitary-cell studies from the 1980s and 1990s showed that GHRH-receptor and secretagogue-receptor inputs release growth hormone synergistically. No published study tests the commercial blend itself; the pairing rests on that older receptor-level work.

Are CJC-1295 or ipamorelin approved by the FDA?

No. Neither is an approved drug anywhere. CJC-1295's ConjuChem program and ipamorelin's Novo Nordisk and Helsinn programs did not reach approval. Both appear on the WADA Prohibited List, and research vials are supplied only for in vitro laboratory use.

Citations

1. Jetté L, Léger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058. PMID 15817669
2. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PMID 17018654
3. Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-E1294. PMID 16822960
4. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res. 2009;19(6):471-477. PMID 19386527
5. Su CM, Jensen LR, Heimer EP, et al. In vitro stability of growth hormone releasing factor (GRF) analogs in porcine plasma. Horm Metab Res. 1991;23(1):15-21. PMID 1826667
6. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. PMID 9849822
7. Johansen PB, Hansen KT, Andersen JV, et al. Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption. Xenobiotica. 1998;28(11):1083-1092. PMID 9879640
8. Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. J Pharmacol Exp Ther. 2009;329(3):1110-1116. PMID 19289567
9. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. PMID 8688086
10. Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PMID 1333056
11. Cheng J, Wu TJ, Butler B, Cheng K. Growth hormone releasing peptides: a comparison of the growth hormone releasing activities of GHRP-2 and GHRP-6 in rat primary pituitary cells. Life Sci. 1997;60(16):1385-1392. PMID 9096259
12. Bowers CY. History to the discovery of ghrelin. Methods Enzymol. 2012;514:3-32. PMID 22975043
13. Timms M, Ganio K, Steel R. A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS. Drug Test Anal. 2019;11(8):1248-1257. PMID 30938069

This article is for laboratory research reference only. US Prime Peptides products are supplied strictly for in vitro research. Not for human consumption.

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