Mechanism of action
CJC-1295 (no DAC) acts as an agonist at the growth hormone-releasing hormone receptor (GHRH-R) on somatotroph cells of the anterior pituitary. Receptor binding activates Gs-protein-coupled signaling (cAMP/PKA) and stimulates the synthesis and release of endogenous growth hormone (GH), which in turn drives hepatic IGF-1 production. The structural basis is the active fragment GRF(1-29) of human GHRH; four substitutions (D-Ala2, Gln8, Ala15, Leu27) increase stability against enzymatic degradation, in particular by dipeptidyl peptidase-4. Unlike the DAC variant, this form carries no maleimidopropionyl linker for covalent binding to serum albumin, so its circulation time remains short. Because somatostatin and IGF-1 continue to exert negative feedback on the axis, the pulsatile pituitary secretion pattern is in principle preserved, a distinction from administration of exogenous GH. Preserved pulsatility has, however, only been observed for the DAC variant, where basal GH levels rose markedly at the same time (Ionescu and Frohman, 2006); no such data exist for the DAC-free form.
State of evidence
The published human evidence largely concerns not this form but the albumin-binding DAC variant. Teichman et al. (JCEM 2006) studied CJC-1295 with DAC in randomized, placebo-controlled early-phase trials in healthy adults and reported dose-dependent increases in GH and IGF-1 as well as an estimated half-life of 5.8 to 8.1 days; Ionescu and Frohman (JCEM 2006) described preserved pulsatility of GH secretion for the same substance. The preclinical work in pituitary cell cultures and rat models (Jetté et al., Endocrinology 2005) and in the GHRH knockout mouse (Alba et al., 2006) likewise concerns the albumin-binding conjugate; Jetté et al. compared it with unmodified hGRF(1-29), not with the DAC-free tetrasubstituted form. For the DAC-free form itself, no published controlled human trials exist. The widely cited half-life of roughly 30 minutes for this short-acting form is not documented in any of the primary sources cited here; the value measured by Teichman et al. belongs to the DAC variant and cannot be transferred to it. No marketing authorization exists in the EU or the United States, and the substance class is prohibited by WADA (Memdouh et al., 2021). Phase 2 and phase 3 data, long-term safety and endpoint studies are absent.
Storage and handling
Lyophilized peptides are generally stored cool, dry, and protected from light in a sealed container. After reconstitution with a suitable solvent, the solution is typically kept refrigerated (2 to 8 °C) and used within a few days. These are generic handling notes for lyophilized peptides, not product-specific stability data.
Questions about the research
- What is CJC-1295 (no DAC) studied for in research?
- The focus is the growth hormone axis: as a GHRH analog, the substance addresses the pituitary GHRH receptor and thereby the release of endogenous GH and downstream IGF-1 production. At this level, research examines receptor binding, stability against enzymatic degradation, and the secretion pattern compared with unmodified GRF(1-29). A second line of work is analytical and concerns the detection of GHRH analogs in doping control.
- What is the state of the evidence on CJC-1295 (no DAC)?
- It is thin and largely concerns a different molecular form. Controlled human data exist for the DAC variant from early-phase trials, but not for the DAC-free form; the preclinical work in cell culture and rodent models usually cited alongside it also concerns the albumin-binding conjugate. There is no approval in the EU or the United States, no phase 3 data and no long-term safety data, so no conclusions about efficacy or safety can be drawn from this evidence.
Sources
- Teichman et al., J Clin Endocrinol Metab 2006DOI: 10.1210/jc.2005-1536PMID: 16352683
- Ionescu & Frohman, J Clin Endocrinol Metab 2006DOI: 10.1210/jc.2006-1702PMID: 17018654
- Jetté et al., Endocrinology 2005DOI: 10.1210/en.2004-1286PMID: 15817669
- Alba et al., Am J Physiol Endocrinol Metab 2006DOI: 10.1152/ajpendo.00201.2006PMID: 16822960
- Memdouh et al., Drug Test Anal 2021DOI: 10.1002/dta.3183PMID: 34665524
