CJC-1295 No DAC

CJC-1295 No DAC (also known as Mod GRF 1-29 or Modified GRF) is a synthetic 29-amino acid peptide analog of growth hormone-releasing hormone (GHRH). It corresponds to the first 29 amino acids of GHRH with four amino acid substitutions (positions 2, 8, 15, and 27) designed to improve metabolic stability by conferring resistance to dipeptidyl peptidase IV (DPP-IV) cleavage and other enzymatic degradation. Unlike CJC-1295 with DAC, this version does not contain a Drug Affinity Complex and therefore does not bind albumin, resulting in a shorter half-life that better mimics the pulsatile nature of endogenous GHRH release. The peptide activates the GHRH receptor (GHRHR) on pituitary somatotrophs, stimulating growth hormone synthesis and secretion in a physiological pulsatile pattern.

CJC-1295 No DAC has been investigated for its agonist activity at the GHRH receptor on anterior pituitary somatotroph cells. Researchers observed that binding to GHRHR activates Gs-coupled adenylyl cyclase, increasing intracellular cAMP levels and activating protein kinase A (PKA). This signaling cascade promotes both GH gene transcription and secretory vesicle exocytosis of stored growth hormone. Unlike the DAC-conjugated version, CJC-1295 No DAC has a half-life of approximately 30 minutes, which produces discrete GH pulses rather than sustained elevation. Studies suggest this pulsatile pattern more closely mimics the endogenous GHRH rhythm and may preserve the physiological GH feedback axis. In preclinical and clinical studies, researchers observed that CJC-1295 No DAC is most effective when combined with a GHSR agonist (such as ipamorelin), as GHRH and ghrelin-mimetic signaling act synergistically at the pituitary level to amplify GH release.

Modified GRF Stability

Ling et al. (1984) characterized structure-activity relationships in GHRH analogs, establishing that the first 29 amino acids contain the full biological activity and that specific substitutions can confer resistance to enzymatic degradation [1].

GHRH Receptor Pharmacology

Gaylinn BD (2002) reviewed the molecular pharmacology of the GHRH receptor, including signaling cascades, receptor desensitization, and the rationale for pulsatile versus continuous GHRH receptor stimulation [2].

Synergy with GHSR Agonists

Bowers et al. (1990) demonstrated the synergistic effect of GHRH and GH secretagogues on pituitary GH release, showing that combined administration produced GH responses greater than the sum of individual treatments [3].