Overview
CJC-1295 with DAC is the long-acting growth hormone-releasing factor analogue first described in 2005: a tetrasubstituted human GRF(1-29) with an added C-terminal lysine carrying an Nε-3-maleimidopropionamide group, the drug affinity complex (DAC)1. The maleimide reacts with the free thiol on Cys34 of serum albumin, forming a covalent bioconjugate that extends plasma persistence1,6.
It is distinct from CJC-1295 without DAC (modified GRF 1-29), which lacks the albumin-binding lysine, and findings for one form do not transfer directly to the other. Published work includes the originating rat studies, a GHRH knockout mouse model, two early clinical pharmacology studies described here by design only, and anti-doping detection methods1,2,3,4,5,6.
Mechanism of action
As described in the research literature
As described in the research literature, three maleimido derivatives of hGRF(1-29) were bioconjugated to human serum albumin ex vivo; all showed enhanced stability against dipeptidyl peptidase-IV and were active in a growth hormone secretion assay in cultured rat anterior pituitary cells1. In rats, CJC-1295 was detected in plasma beyond 72 hours, and western blotting showed CJC-1295 immunoreactivity on the serum albumin band from 15 minutes onwards1.
In GHRH knockout mice, CJC-1295 was associated with increased total pituitary RNA and GH mRNA, with immunohistochemistry suggesting somatotroph proliferation2. Because the albumin conjugate provides sustained rather than pulsed GRF receptor stimulation, one study used frequent overnight blood sampling to examine whether growth hormone secretory pulses persist under these conditions4.
Research areas
What published studies have examined
Albumin bioconjugation in rats
Maleimido derivatives of hGRF(1-29) were compared for stability against dipeptidyl peptidase-IV, activity in rat pituitary cell culture and growth hormone release in rats, and CJC-1295 was selected for pharmacokinetic evaluation, including western blot detection of the albumin conjugate1.
Sources [1]
GHRH knockout mouse model
Mice lacking the GHRH gene were used to examine body weight and length, femur and tibia length, body composition, pituitary RNA and GH mRNA, comparing different study protocols2.
Sources [2]
Clinical pharmacology studies
Two randomised, placebo-controlled, double-blind studies examined pharmacokinetics, with GH and IGF-I as the main outcome measures3, and a separate study examined the frequency and magnitude of GH secretory pulses4. They are noted here by design only.
Sources [3] [4]
Analytical detection
In vitro metabolites of sermorelin, tesamorelin and CJC-1295 with and without DAC were identified, synthesised and used to develop a urine detection method5. Because albumin conjugation prevents detection by top-down mass spectrometry, an immuno-PCR assay was developed to detect the CJC-1295 protein conjugate in equine plasma6.
Sources [5] [6]
Specifications
- Sequence
- 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(Nε-3-maleimidopropionyl)-NH2
- Molecular formula
- C165H269N47O46
- Molecular weight
- 3647.2 g/mol
- CAS number
- 446262-90-4
- Form
- White to off-white lyophilised powder in a sealed vial
- Storage
- Store lyophilised powder at -20 °C, protected from light and moisture. Once reconstituted, keep refrigerated at 2 to 8 °C and protect from light.
- Solubility and reconstitution
- Reconstitute with bacteriostatic water. Add the diluent slowly down the inside wall of the vial and swirl gently until clear; do not shake.
References
- 1
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.
Jetté L, Léger R, Thibaudeau K, et al. Endocrinology, 2005.
PubMed 15817669 ↗DOI 10.1210/en.2004-1286 ↗
- 2
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.
Alba M, Fintini D, Sagazio A, et al. American Journal of Physiology. Endocrinology and Metabolism, 2006.
PubMed 16822960 ↗DOI 10.1152/ajpendo.00201.2006 ↗
- 3
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.
Teichman SL, Neale A, Lawrence B, et al. The Journal of Clinical Endocrinology and Metabolism, 2006.
PubMed 16352683 ↗DOI 10.1210/jc.2005-1536 ↗
- 4
Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog.
Ionescu M, Frohman LA The Journal of Clinical Endocrinology and Metabolism, 2006.
PubMed 17018654 ↗DOI 10.1210/jc.2006-1702 ↗
- 5
- 6
An immuno polymerase chain reaction screen for the detection of CJC-1295 and other growth-hormone-releasing hormone analogs in equine plasma.
Timms M, Ganio K, Forbes G, et al. Drug Testing and Analysis, 2019.
PubMed 30489688 ↗DOI 10.1002/dta.2554 ↗