CJC-1295 (No DAC)

Mechanism of action in research models

CJC-1295 (No DAC) is a high-affinity agonist of the GHRH receptor (GHRHR), a class-B (secretin family) GPCR predominantly expressed on pituitary somatotroph cells. Agonist binding activates Gs-coupled adenylyl cyclase, generating cAMP and activating PKA — the primary intracellular signal driving GH synthesis and secretory-granule exocytosis. The GHRHR-cAMP-PKA axis also activates the transcription factor Pit-1/GHF-1, promoting GH gene transcription and amplifying somatotroph GH content over time.

In contrast to GHSR-1a (ghrelin-receptor) agonists like Ipamorelin, which primarily trigger calcium-mediated GH exocytosis, GHRHR agonism by CJC-1295 (No DAC) works predominantly through the adenylyl-cyclase/cAMP pathway. The two pathways converge on GH secretion but through distinct second-messenger systems — the mechanistic basis for their documented synergistic interaction in combination research protocols.

DPP-IV resistance is central to research utility: native GHRH(1-29) is cleaved by DPP-IV at the Ala2-Asp3 bond within seconds in biological fluids, rendering it essentially inactive as an experimental agent without continuous infusion. The Aib2 substitution makes this bond inaccessible to DPP-IV, generating a GHRH analogue with a far more extended research window while still providing a pulse-duration action distinguishable from the ultra-long DAC-bearing form.

Research background and peer-reviewed literature

The development of CJC-1295 (No DAC) belongs to a lineage of GHRH-analogue research that began with the characterisation of native GHRH by the Guillemin and Vale/Rivier laboratories in 1982. Structure-activity studies through the 1980s–2000s established which substitutions preserve receptor affinity while improving stability, culminating in the tetrakis-substituted CJC series.

A key publication from the Teichman group described CJC-1295 (without DAC) in combination with CJC-1295-DAC in human research volunteers, documenting dose-dependent GH and IGF-1 increases. The non-DAC form produced GH pulses of shorter duration than the DAC form, confirming the pharmacokinetic distinction relevant to research study design. Walker et al. published research in rats demonstrating synergistic GH release when CJC-1295 (No DAC) was co-administered with Ipamorelin, supported by in-vitro data from pituitary somatotroph cell preparations — establishing the reference point for combination GHRP/GHRH protocols.

Reconstitution and storage protocol

1. Allow the sealed vial to reach room temperature.
2. Reconstitute with sterile bacteriostatic water or another validated research diluent. CJC-1295 (No DAC) is well-soluble in water; 1 mg/mL is a practical research concentration.
3. Add diluent slowly along the vial wall; swirl gently until clear.
4. Reconstituted solution should be clear and colourless.

Storage: lyophilized at −20 °C, sealed, desiccated, light-protected (stable 24+ months). Reconstituted at 4 °C for up to 28 days in bacteriostatic water; aliquot to −80 °C for extended storage.