CJC-1295 (With DAC)

CJC-1295 With DAC is the albumin-conjugating variant of the four-modification GHRH(1-29) analogue, incorporating the Drug Affinity Complex (DAC) technology — a maleimidopropionic acid reactive group that undergoes irreversible covalent thiol-Michael addition with Cys-34 of serum albumin. The resulting succinimide thioether linkage is stable under physiological conditions, creating a peptide-albumin conjugate whose effective half-life of approximately 8 days reflects albumin catabolism kinetics rather than peptide-specific clearance.

The chemistry of DAC conjugation is site-specific and irreversible. Albumin contains 35 cysteine residues, of which 34 are paired in disulphide bonds. The single free thiol — Cys-34 (also designated Cys-34 in the standard albumin numbering) — is the unique reactive site for maleimide-thiol chemistry under physiological conditions. Within minutes of entering the bloodstream, CJC-1295 With DAC's maleimide group reacts with albumin Cys-34, converting the entire peptide pool to albumin-bound form. The FcRn (neonatal Fc receptor) recycling pathway that protects albumin from lysosomal degradation then maintains the peptide-albumin conjugate for its approximately 8-day lifespan.

This mechanism produces fundamentally different pharmacokinetics from non-covalent albumin-binding strategies used by fatty acid-conjugated peptides. Semaglutide and similar compounds maintain a dynamic equilibrium between free and albumin-bound forms — the free fraction is what activates receptors, and the albumin dissociation rate determines the effective concentration of bioavailable peptide. CJC-1295 With DAC has no free equilibrium fraction: the entire dose is immediately and permanently albumin-bound. Receptor activation requires either albumin to directly present the peptide to GHRHR on pituitary cell surfaces, or peptide release during albumin catabolism in lysosomes.

The landmark Ionescu and Frohman (JCEM, 2006) clinical pharmacology study established the counterintuitive finding that GH secretion remains pulsatile even during continuous GHRHR stimulation from CJC-1295 With DAC. Rather than producing a constant, sustained GH elevation, the extended GHRHR occupancy maintains high somatotroph responsiveness while GH pulse timing continues to be governed by the rhythmic hypothalamic somatostatin pacemaker — somatostatin neurons fire every 3-4 hours, periodically suppressing GH despite continuous GHRHR activation, then releasing GH in amplified pulses during the somatostatin-withdrawal windows.

For in vitro research, CJC-1295 With DAC requires serum-free conditions for predictable pharmacology. In serum-containing media, the maleimide immediately conjugates to albumin in the serum, converting free peptide to albumin-bound form before it reaches GHRHR. Use serum-free defined media for CJC-1295 With DAC concentration-response experiments, or switch to CJC-1295 No DAC (which remains as a free peptide in all media types) for routine in vitro GHRHR pharmacology.

Research paradigms uniquely enabled by CJC-1295 With DAC's extended half-life: chronic GH axis stimulation studies in rodent models without repeated dosing; comparison of acute pulsatile (CJC-1295 No DAC) versus sustained (With DAC) GHRHR stimulation effects on downstream IGF-1 production and body composition; and GHRHR desensitisation kinetics under prolonged agonist occupancy.

MW: approximately 3647 g/mol (free peptide). Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. Reconstitute immediately before use to minimise maleimide hydrolysis. For laboratory and analytical research purposes only.

Key research paradigms uniquely enabled by CJC-1295 With DAC: chronic GH axis stimulation studies without repeated dosing; comparison of pulsatile (No DAC) versus sustained (With DAC) GHRHR stimulation effects on body composition and IGF-1 production kinetics; and GHRHR desensitisation kinetics under prolonged agonist occupancy in primary pituitary cell preparations. Reconstitute in bacteriostatic water immediately before use to minimise maleimide hydrolysis. MW: approximately 3647 g/mol. Store lyophilised at -20°C. For laboratory and analytical research purposes only.