CJC-1295 is a long-acting GHRH analogue and ipamorelin is a selective ghrelin mimetic. Research on each compound and their studied effects on GH secretion profiles.
The growth hormone (GH) axis involves a tightly regulated interplay between hypothalamic hormones and the pituitary gland. Growth hormone-releasing hormone (GHRH), produced in the hypothalamus, stimulates pituitary somatotrophs to secrete GH in pulsatile bursts. GH then acts on peripheral tissues and stimulates hepatic insulin-like growth factor-1 (IGF-1) secretion.
Two synthetic peptides studied extensively in this context are CJC-1295, a modified GHRH analogue, and ipamorelin, a selective growth hormone secretagogue (GHS). Each targets distinct receptors within the GH axis and produces different secretion kinetics, making their pharmacological profiles of independent research interest.
Full Name: CJC-1295 (with DAC: Drug Affinity Complex)
CAS Number: 863288-34-0
Molecular Weight: 3647.1 Da
Mechanism: GHRH receptor agonist
CJC-1295 is a tetrasubstituted 29-amino acid peptide analogue of endogenous GHRH(1-29). The native GHRH(1-29) peptide has a plasma half-life of only 5-7 minutes due to dipeptidyl peptidase IV (DPP-IV) cleavage at Ala2. CJC-1295 incorporates four amino acid substitutions to confer DPP-IV resistance and introduces a maleimidoproprionic acid (MPA) side chain that facilitates covalent binding to circulating albumin (the Drug Affinity Complex, or DAC modification).
This albumin-binding strategy dramatically extends the pharmacokinetic profile. In a randomised, double-blind Phase 1 trial in healthy adults, a single subcutaneous injection of CJC-1295 produced sustained elevation of plasma GH and IGF-1, with a terminal half-life of 5.8 to 8 days (Teichman et al., 2006).
A key research question was whether continuous GHRH receptor stimulation from a long-acting analogue would suppress normal pulsatile GH secretion, as is observed with continuous GHRH infusion. Ionescu and Frohman (2006) examined GH secretion profiles in healthy adults following CJC-1295 administration and found that pulsatile GH secretion was preserved throughout the study period, with mean pulse amplitude and frequency remaining within normal ranges. This preservation of physiological secretion patterns distinguishes CJC-1295 from continuous GHRH infusion paradigms.
In the Teichman et al. (2006) study, mean IGF-1 levels increased by 20-30% from baseline following CJC-1295, with the elevation sustained for up to two weeks after a single injection. Multiple doses produced cumulative increases of 40-60%. These pharmacodynamic characteristics make CJC-1295 a useful research tool for investigating sustained GH axis stimulation without requiring repeated daily dosing.
CAS Number: 170851-70-4
Molecular Weight: 711.85 Da
Mechanism: Ghrelin receptor (GHS-R1a) agonist; selective growth hormone secretagogue
Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) and belongs to the growth hormone secretagogue (GHS) class. It acts at the ghrelin receptor (GHS-R1a) in the hypothalamus and pituitary to stimulate GH release through a pathway distinct from the GHRH receptor.
The compound was characterised by Raun et al. (1998) as the first highly selective GHS compound: it stimulates GH release at potencies comparable to GHRP-6 but without significant effects on ACTH, cortisol, prolactin, FSH, or LH in rodent and swine models. This selectivity is a defining pharmacological feature that distinguishes ipamorelin from earlier GHS compounds.
Earlier GHS compounds such as GHRP-6 and GHRP-2 stimulate GH release but also elevate plasma cortisol and prolactin concentrations. This limits their utility as specific tools for studying the GH axis in isolation. Ipamorelin's selectivity for the ghrelin receptor without concomitant ACTH/cortisol stimulation makes it a more specific research tool for GH secretion studies (Raun et al., 1998).
Raun et al. (1998) characterised ipamorelin's dose-response relationship in anaesthetised rats and conscious swine. GH release was dose-dependent across the range studied, with maximum GH output comparable to that achieved by combined GHRH and GHRP-6 co-administration. Importantly, cortisol and prolactin remained unchanged across all doses, confirming the selectivity profile.
The combination of CJC-1295 and ipamorelin has been studied on the rationale that GHRH receptor activation (via CJC-1295) and GHS-R1a activation (via ipamorelin) represent synergistic rather than redundant pathways. In-vitro and animal studies have demonstrated supra-additive GH release when both pathways are activated simultaneously, consistent with the known synergy between GHRH and ghrelin signalling in somatotroph physiology.
The pharmacokinetic profiles also complement each other: CJC-1295's long half-life elevates baseline GH tone, while ipamorelin provides acute pulsatile GH release during the combination period.
| Property | CJC-1295 | Ipamorelin |
|---|---|---|
| Receptor Target | GHRH-R | GHS-R1a (ghrelin receptor) |
| Peptide Length | 29 amino acids | 5 amino acids (pentapeptide) |
| Half-life | 5.8-8 days | ~2 hours |
| Selectivity | GHRH pathway | GH-selective (no ACTH/cortisol effect) |
| Research Model | Human Phase 1 trials | Rat and swine models |
1. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. "Prolonged Stimulation of Growth Hormone (GH) and Insulin-like Growth Factor I Secretion by CJC-1295, a Long-Acting Analog of GH-Releasing Hormone, in Healthy Adults." *Journal of Clinical Endocrinology and Metabolism.* 2006;91(3):799-805.
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." *Journal of Clinical Endocrinology and Metabolism.* 2006;91(12):4792-4797.
3. Raun K, Hansen BS, Johansen NL, Thogersen H, Madsen K, Ankersen M, Andersen PH. "Ipamorelin, the First Selective Growth Hormone Secretagogue." *European Journal of Endocrinology.* 1998;139(5):552-561.
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