CJC-1295
Also known as: Modified GRF 1-29, Mod GRF 1-29, CJC-1295 DAC, Sermorelin analog
A GHRH analog engineered for extended half-life, studied for its ability to stimulate sustained pulsatile growth hormone release.
Molecular Data
- Class
- GHRH analog / Growth hormone secretagogue
- Molecular Weight
- ~3,367 Da (without DAC) / ~3,647 Da (with DAC)
- Molecular Formula
- C₁₅₂H₂₅₂N₄₄O₄₂ (without DAC); ~C₁₅₇H₂₆₀N₄₄O₄₅ (with DAC, approximate)
- Half-Life
- ~30 minutes (without DAC) / ~6–8 days (with DAC)
- Sequence / Structure
- 30-amino acid modified hGHRH 1-29 analog; substitutions at positions 2, 8, 15, 27; MPA-albumin binding moiety in DAC form
Mechanism of Action
CJC-1295 is a synthetic 30-amino acid analog of growth hormone-releasing hormone (GHRH), also called growth hormone-releasing factor (GRF). It was designed as a modified version of the first 29 amino acids of human GHRH (hGHRH 1–29) — the minimal sequence required for full biological activity.
Pituitary GHRH receptor activation: CJC-1295 binds to GHRH receptors on somatotroph cells in the anterior pituitary with high affinity, stimulating the synthesis and pulsatile release of growth hormone. Unlike direct GH administration, GHRH agonists preserve the natural pulsatile GH secretion pattern and the regulatory feedback loop through somatostatin.
Structural modifications for half-life extension: - The native hGHRH 1–29 (Sermorelin) has a half-life of ~7–8 minutes in plasma, limiting practical utility. - CJC-1295 incorporates 4 amino acid substitutions (at positions 2, 8, 15, and 27) that reduce susceptibility to dipeptidyl peptidase IV (DPP-IV) and other plasma proteases, extending the half-life to ~30 minutes. - The variant known as CJC-1295 with DAC (Drug Affinity Complex) adds a maleimidopropionic acid (MPA) group that forms a stable, covalent amide bond with plasma albumin following injection. This albumin binding dramatically extends the effective half-life to approximately 6–8 days and has been the primary subject of clinical investigation.
Downstream effects studied: - Stimulation of pulsatile GH secretion from the pituitary - Elevated IGF-1 (insulin-like growth factor 1) levels, reflecting increased hepatic GH signaling - Potential anabolic, lipolytic, and recovery effects investigated in the context of GH axis research
Research History
CJC-1295 was developed by ConjuChem Biotechnologies (Montreal) in the mid-2000s as a next-generation GHRH analog intended to overcome the very short half-life of Sermorelin (hGHRH 1–29), which required twice-daily subcutaneous dosing.
The pivotal early clinical study by Ionescu and Frohman (2006) in the Journal of Clinical Endocrinology & Metabolism evaluated CJC-1295 with DAC in 21 healthy adults. Single-dose injection produced dose-dependent increases in mean serum GH (2- to 10-fold over baseline) that persisted for up to 6 days, and correspondingly elevated IGF-1 levels that remained elevated for up to 14 days. This demonstrated the pharmacokinetic feasibility of once-weekly GHRH agonist dosing.
ConjuChem advanced CJC-1295 into Phase II clinical trials but the company later encountered financial difficulties. As of 2024, CJC-1295 has not received regulatory approval for any indication, and no large-scale randomized controlled trials have been completed.
In the research community, CJC-1295 (both with and without DAC) has been widely used in preclinical GH axis studies. The "without DAC" variant (often called Mod GRF 1-29) has a shorter half-life and is frequently combined with ghrelin mimetics such as GHRP-2 or Ipamorelin in rodent studies to examine synergistic effects on GH pulsatility.
Notable Studies
Long-acting growth hormone releasing factor (CJC-1295) in normal men
2006Ionescu M, Frohman LA · Journal of Clinical Endocrinology & Metabolism
Pivotal Phase I/II human study (n=21) demonstrating that a single injection of CJC-1295 with DAC produced sustained 2- to 10-fold GH elevations lasting up to 6 days and IGF-1 increases persisting 14 days, with good tolerability.
CJC-1295, a long-acting growth hormone-releasing factor analog
2005Jetté L, Léger R, Thibaudeau K, et al. · Endocrinology
Preclinical characterization of CJC-1295 pharmacokinetics in rats, demonstrating the albumin-binding mechanism and extended half-life compared to native GRF analogs.
Sermorelin (GHRH 1-29) in adults with growth hormone deficiency: a systematic review
1999Prakash A, Goa KL · Drugs & Aging
Systematic review of the predecessor compound sermorelin, providing context for GHRH-class pharmacology; CJC-1295 was designed to address the short half-life limitation documented in this evidence base.
Research Protocols
The following protocols describe doses used in published research studies. They are not prescriptions or recommendations for human use.
Ionescu & Frohman 2006 clinical study
- Dose
- 30–60 µg/kg (single dose)
- Route
- Subcutaneous injection
- Frequency
- Single injection per study arm
- Duration
- Single-dose PK/PD study; GH/IGF-1 measured for 28 days
This is the primary human PK/PD data for CJC-1295 with DAC; multi-dose effects have not been characterized in a large clinical trial.
Rodent GH axis studies (without DAC / Mod GRF 1-29)
- Dose
- 1–2 µg/kg
- Route
- Intravenous or subcutaneous
- Frequency
- Pulsed administration to mimic physiological GHRH release
Often co-administered with ghrelin mimetics (GHRP-2, Ipamorelin) in rodent experiments to assess synergistic effects on GH pulse amplitude.