Product description
What is CJC-1295 with DAC?
CJC-1295 with DAC (Drug Affinity Complex) is a synthetic analogue of growth hormone-releasing hormone (GHRH), developed by ConjuChem Biotechnologies. The full name is DAC:GRF (Drug Affinity Complex:Growth Hormone-Releasing Factor).
The peptide is a modified version of the GHRH(1-29) fragment, also known as sermorelin, with four amino acid substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) increasing resistance to enzymatic degradation and with added at the C-terminus, a DAC - lysine moiety with a maleimidopropionyl linker attached. The sequence is: H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser- Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys(Maleimidopropionyl)-NH₂.
The key feature of CJC-1295 is the albumin binding complex (DAC) - the maleimidopropionyl moiety on the C-terminal lysine covalently binds to the free thiol group of endogenous serum albumin after injection. This binding to albumin (t½ albumin ≈20 days) dramatically increases the half-life of the peptide from minutes (native GHRH) to 5.8-8.1 days in humans.
A clear distinction must be made between CJC-1295 with DAC and CJC-1295 without DAC (also called Modified GRF 1-29 or MOD-GRF) - the latter form does not contain an albumin-binding moiety and has a short half-life (~30 minutes).
Mechanism of action
CJC-1295 acts as a selective GHRH receptor (GHRH-R) agonist on somatotropic cells of the anterior pituitary:
Stimulation of growth hormone (GH) secretion – Binding of CJC-1295 to the GHRH receptor activates the cAMP/PKA signaling cascade, leading to the synthesis and release of growth hormone (somatotropin) from the pituitary. Unlike direct GH supplementation, stimulation by CJC-1295 preserves the physiological pulsatility of GH secretion, which is believed to be important for many of the hormone's biological effects.
Prolonged DAC stimulation – Albumin-binding complex provides continuous, low-level stimulation of the GHRH receptor for many days after a single injection. In clinical studies, a single dose of CJC-1295 increased mean plasma GH concentrations 2-10-fold for 6 days or longer.
Preservation of GH pulsatility – Despite continuous GHRH stimulation, GH secretion remains pulsatile, although with increased pulse amplitude and increased basal level (throughput). Analysis of nocturnal 12-hour blood sampling (every 20 minutes) in healthy men showed preserved pulsatility with a 7.8-fold increase in interpulse levels.
IGF-1 increase – Stimulation of the GH axis leads to a secondary increase in the concentration of insulin-like growth factor 1 (IGF-1) in the liver and peripheral tissues. After a single injection of CJC-1295, IGF-1 concentration increased 1.5-3-fold and remained elevated for 9-11 days. After repeated doses, IGF-1 levels remained elevated for at least 28 days.
Cumulative effect – Repeated administration of CJC-1295 showed a cumulative effect on IGF-1 stimulation, suggesting the possibility of achieving stable, elevated levels with regular dosing.
Directions of scientific research
CJC-1295 has been the subject of Phase I and II clinical trials, primarily for its potential use in growth hormone deficiency and lipodystrophy.
Pharmacokinetic and pharmacodynamic studies in healthy adults
The key study by Teichman et al. (2006) included two randomized, double-blind, placebo-controlled, escalating-dose studies in healthy adults (21–61 years). In the first study (28 days), single subcutaneous doses were administered, in the second (49 days) - 2-3 weekly or biweekly doses. The results showed:
- Dose-dependent increase in GH (2-10-fold) lasting ≥6 days
- IGF-1 increase (1.5-3-fold) lasting 9-11 days
- Half-life 5.8-8.1 days
- Cumulative effect with repeated dosing
- Good tolerance at doses of 30-60 µg/kg
Studies on GH pulsatility
The study by Ionescu and Frohman (2006) examined in detail the effect of CJC-1295 on pulsatile GH secretion. In healthy men (20-40 years of age), overnight 12-hour blood sampling was performed before and one week after injection of 60 or 90 µg/kg CJC-1295. Preserved pulsatility was demonstrated with:
- Increase in average GH secretion
- Significant increase in basic levels (through)
- Correlation between the increase in trough GH and the increase in IGF-1
Studies on animal models of GHRH deficiency
In a GHRH gene knockout (GHRHKO) mouse model, daily administration of CJC-1295 (2 µg) for 5 weeks normalized body weight, body length, femur and tibia length, and body composition (fat and fat-free mass). The peptide also increased pituitary total RNA and growth hormone mRNA, which suggested somatotropic cell proliferation. The same dose given every 48 or 72 hours was less effective.
Proteomics studies
Proteomic analysis of serum from healthy men before and after CJC-1295 administration showed changes in 5 proteins: a decrease in the apolipoprotein A1 isoform and transthyretin and an increase in beta-hemoglobin and albumin fragments. A correlation was observed between some proteins and IGF-1 levels, suggesting potential biomarkers of GH/IGF-1 action.
Clinical development status
CJC-1295 has reached Phase II clinical trials for lipodystrophy and growth hormone deficiency, but development was interrupted after the death of one of the study participants. The attending physician assessed that the most likely cause was asymptomatic coronary artery disease with rupture of atherosclerotic plaque, unrelated to CJC-1295 treatment. Despite this assessment, the development program was not resumed.
Scientific context
CJC-1295 represents a strategy to prolong the action of therapeutic peptides through bioconjugation with endogenous proteins (in this case, albumin). A similar approach has been used in other peptides (e.g. semaglutide binding to albumin via fatty acid acylation).
Compared to other GH secretagens:
- Native GHRH – t½ 7-10 minutes, requires continuous infusion or frequent administration
- Sermorelin (GHRH 1-29) – t½ ~10-20 minutes, historically approved for the treatment of GH deficiency in children (withdrawn for manufacturing reasons in 2008)
- Tesamorelin – modified GHRH, FDA registered as Egrifta® for the treatment of HIV-related lipodystrophy
- CJC-1295 without DAC (MOD-GRF 1-29) – t½ ~30 minutes, requires multiple daily administration
- CJC-1295 with DAC – t½ 5.8-8.1 days, potentially once weekly administration
CJC-1295 with DAC is often compared to ghrelin receptor (GHS) secretogens such as ipamorelin or MK-677, which act through a different mechanism (GHS-R1a receptor). Theoretically, the GHRH + GHS combination may show synergy, although clinical data are limited.
Research safety profile
In published clinical studies, CJC-1295 was generally well tolerated, particularly at doses of 30-60 µg/kg. Reported adverse events included:
Common (dose-dependent):
- Injection site reactions (redness, pain)
- Sudden facial flushing (flushing)
- Headaches
- Diarrhea
Rare:
- Drowsiness and fatigue (WHO grade II at a dose of 0.03 mg/kg in 1/2 of subjects)
- Peripheral edema
- Paresthesia
No serious adverse events were reported in the published Phase I studies. One death during the Phase II studies was probably unrelated to treatment (asymptomatic coronary artery disease).
CJC-1295 and other GHRH analogues are on the WADA (World Anti-Doping Agency) list of prohibited substances in sports.
Bibliography - latest scientific research
- Teichman SL, Neale A, Lawrence B, et al. 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. J Clin Endocrinol Metab. 2006;91(3):799-805. PubMed
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analogue. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PubMed
- 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. PubMed
- Sackmann-Sala L, Ding J, Frohman LA, Bhatti TR. 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. PMC
- Memdouh Z, Thieme D, Keiler AM, et al. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Test Anal 2022;14(1):76-90. PubMed
- Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sex Med Rev. 2018;6(1):45-53. PubMed
- Clemmons DR. Long-Acting Forms of Growth Hormone-Releasing Hormone and Growth Hormone: Effects in Normal Volunteers and Adults with Growth Hormone Deficiency. Horm Res 2007;68(Suppl 5):178-181. PubMed
- Thomas A, Thevis M, Delahaut P, et al. Mass spectrometric identification of degradation products of insulin and its long-acting analogues in human urine for doping control purposes. Anal Chem. 2007;79(6):2518-2524. PubMed
- Holt RI, Sönksen PH. Growth hormone, IGF-I and insulin and their abuse in sport. Br J Pharmacol. 2008;154(3):542-556. PMC
- Junnila RK, List EO, Berryman DE, et al. The GH/IGF-1 axis in aging and longevity. Nat Rev Endocrinol. 2013;9(6):366-376. PMC
