CJC-1295

CJC-1295 is a synthetic peptide analogue of growth hormone-releasing hormone (GHRH), specifically a modified version of the first 29 amino acids of endogenous GHRH (GRF 1-29). The peptide incorporates four amino acid substitutions that confer resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), which normally cleaves and inactivates native GHRH within minutes. CJC-1295 exists in two forms: with a Drug Affinity Complex (DAC) that binds serum albumin to extend half-life to approximately 6-8 days, and without DAC (commonly called Mod GRF 1-29) which retains a shorter half-life of roughly 30 minutes.

The peptide was developed by ConjuChem Biotechnologies and reached Phase II clinical trials for growth hormone deficiency and lipodystrophy before development was discontinued. It remains one of the most studied GHRH analogues and is frequently used in research settings, often in combination with GH-releasing peptides (GHRPs) to produce synergistic GH release through dual receptor activation.

CJC-1295 acts as a full agonist at the GHRH receptor (GHRHR), a class B G protein-coupled receptor expressed on somatotroph cells in the anterior pituitary. Receptor activation stimulates adenylyl cyclase, increasing intracellular cAMP and activating protein kinase A, which promotes both the synthesis and secretion of growth hormone. This is the same physiological pathway used by endogenous GHRH, meaning CJC-1295 works with the existing feedback architecture rather than overriding it — somatostatin tone still modulates the GH response, which is why the non-DAC version better preserves pulsatile release patterns.

The four amino acid substitutions (D-Ala2, Gln8, Ala15, Leu27) protect against DPP-IV cleavage at the N-terminus while preserving receptor binding affinity. In the DAC variant, a reactive maleimido group forms a covalent bond with the thiol group on Cys34 of serum albumin following injection, creating a long-circulating depot. This albumin conjugation is what extends the half-life from minutes to days, enabling once-weekly dosing but at the cost of sustained rather than pulsatile GH elevation.