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CJC-1295 (DAC) vs Ipamorelin / CJC-1295
The single most common point of confusion in GH secretagogue research: CJC-1295 with DAC and CJC-1295 without DAC are different molecules with very different pharmacokinetics. The DAC (Drug Affinity Complex) version conjugates covalently to serum albumin, extending plasma residence to days. The no-DAC form, typically blended with Ipamorelin, clears in hours and produces a pulsatile rather than sustained profile.
CJC-1295 (DAC)
CJC-1295 is a synthetic analog of growth hormone-releasing hormone based on the biologically active N-terminal 1-29 fragment of human GHRH. It acts as an agonist at the GHRH receptor, a class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs, where receptor occupancy elevates intracellular cAMP and promotes synthesis and pulsatile release of endogenous growth hormone, which in turn drives hepatic IGF-1 production. Four amino acid substitutions relative to native GHRH(1-29) confer resistance to enzymatic inactivation, most importantly the D-alanine at position 2, which blocks cleavage by dipeptidyl peptidase-IV, the principal route of GHRH degradation in plasma. The DAC variant additionally carries a maleimidopropionyl group on a C-terminal lysine, which reacts selectively with the free thiol of Cys34 on circulating serum albumin to form a covalent bioconjugate in vivo. Jette and colleagues established this albumin-tethering strategy as the basis for the compound's extended plasma residence, with an estimated half-life of 5.8 to 8.1 days reported in healthy adults by Teichman and colleagues. Because the mechanism acts upstream at the pituitary rather than supplying exogenous growth hormone, output remains subject to negative feedback from somatostatin and IGF-1; Ionescu and Frohman reported that the frequency and magnitude of GH secretory pulses were unaltered despite continuous receptor stimulation, with basal GH rather than pulse amplitude accounting for the increase. CJC-1295 without DAC, commonly marketed as modified GRF 1-29, lacks the maleimide moiety and therefore does not form the albumin conjugate, giving it a fundamentally different pharmacokinetic profile.
Ipamorelin / CJC-1295
This combination targets two distinct but synergistic nodes in the growth hormone (GH) axis. CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH(1–29)) incorporating four amino acid substitutions that confer DPP-4 resistance, extending half-life. The non-DAC version (also known as mod-GRF(1–29)) has a half-life of ~30 minutes, while the DAC (Drug Affinity Complex) version — which covalently binds to plasma albumin via a maleimide linker — has a half-life of approximately 6–8 days, enabling once or twice-weekly dosing. CJC-1295 acts on the GHRH receptor (GHRHR) on pituitary somatotrophs, increasing GH pulse amplitude. Ipamorelin is a selective growth hormone secretagogue pentapeptide that acts as a partial agonist at the ghrelin receptor (GHS-R1a), increasing GH pulse frequency via a distinct intracellular pathway (Gq/PKC rather than Gs/cAMP). Critically, ipamorelin demonstrates high receptor selectivity — it does not appreciably stimulate ACTH, cortisol, or aldosterone release at research doses, unlike older GH secretagogues (GHRP-6, GHRP-2). The synergistic co-administration of CJC-1295 (amplitude) and ipamorelin (frequency) produces GH release patterns that more closely mimic youthful physiological pulsatility and has been shown in preclinical and small human studies to amplify GH and IGF-1 more than either agent alone.
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