CJC-1295 is not one molecule but a name applied to two related research peptides that share the same modified growth hormone-releasing hormone (GHRH) backbone. One version is the unconjugated, tetrasubstituted GHRH(1-29) analog, often labeled Mod GRF 1-29 or "CJC-1295 without DAC." The other carries an added Drug Affinity Complex (DAC), a chemical linker that binds circulating albumin. The DAC is the single structural difference between the two, and it is what the published pharmacokinetic literature points to when explaining why the two forms behave differently in plasma.
| Attribute | CJC-1295 without DAC (Mod GRF 1-29) | CJC-1295 with DAC |
|---|---|---|
| Class | GHRH(1-29) analog | GHRH(1-29) analog with albumin-binding conjugate |
| Backbone length | 29 residues, C-terminal amide | Same 29-residue backbone plus a C-terminal DAC moiety |
| Key substitutions vs. native GHRH | D-Ala2, Gln8, Ala15, Leu27 | Same four substitutions, plus DAC conjugation site |
| What PK studies examined | Structural and regulatory characterization (FDA bulk drug substance review) | Human GH/IGF-I pharmacokinetics and pulsatility (Teichman et al., 2006; Ionescu and Frohman, 2006) |
| Form supplied | Lyophilized powder | Lyophilized powder |
Where does the CJC-1295 backbone come from?
The GHRH backbone used in CJC-1295 traces back to 1982, when two laboratories independently isolated and characterized a growth hormone-releasing factor from a human pancreatic tumor associated with acromegaly (Guillemin et al., 1982; Rivier et al., 1982). The tumor-derived peptide was reported as a 44-amino-acid sequence, and the synthetic replicate was reported to have full biological activity in stimulating growth hormone secretion (Guillemin et al., 1982). The N-terminal 29-residue portion of that sequence, GHRH(1-29), is the fragment later synthetic analogs, including both forms of CJC-1295, are built on.
Why the native fragment needed modification
Native GHRH is short-lived in circulation. In a classic degradation study, human GHRH(1-44)-NH2 incubated with plasma showed a measured half-life of about 63 minutes by radioimmunoassay but disappeared much faster, about 17 minutes, by HPLC, because plasma enzymes rapidly clip the intact peptide into a fragment, GHRH(3-44)-NH2, with less than one-thousandth of the original bioactivity (Frohman et al., 1986). After intravenous injection in human subjects, the same study reported a plasma half-life for intact GHRH(1-44)-NH2 of 6.8 minutes, attributed to a plasma dipeptidylaminopeptidase that removes the first two residues. Because that cleavage occurs after position 2, researchers targeted exactly that position when designing longer-lived analogs.
What is the tetrasubstituted analog, "CJC-1295 without DAC"?
CJC-1295 without DAC is the GHRH(1-29) fragment carrying four amino acid substitutions relative to the native sequence: D-Ala in place of Ala at position 2, Gln in place of Asn at position 8, Ala in place of Gly at position 15, and Leu in place of Met at position 27. The position-2 substitution sits directly at the cleavage site identified in the plasma degradation studies described above, consistent with a design intended to resist the same enzymatic route that inactivates native GHRH. This unconjugated analog is the form referenced throughout the current FDA bulk drug substance review as "CJC-1295 (free base)," distinct from the DAC-conjugated form (FDA Pharmacy Compounding Advisory Committee briefing document, 2024).
What does the Drug Affinity Complex add?
The Drug Affinity Complex is a maleimidopropionic acid group attached to the C-terminus of the same tetrasubstituted GHRH(1-29) backbone. The maleimide reacts with a free thiol on circulating albumin at cysteine 34 (Cys34), forming a covalent peptide-albumin conjugate. Bound to a large, long-circulating plasma protein, the complex is not cleared the way the free peptide is. This is the structural basis researchers cite for the extended plasma persistence reported for the DAC form relative to unconjugated GHRH analogs.
What did published pharmacokinetic studies report about half-life extension?
Two human studies from the same research group form the primary published pharmacokinetic and pharmacodynamic record for CJC-1295 with DAC.
Single- and multiple-dose findings
In two randomized, placebo-controlled, ascending-dose trials in healthy adults, single subcutaneous injections of CJC-1295 with DAC produced dose-dependent increases in mean plasma GH concentrations of 2- to 10-fold persisting 6 days or more, and mean plasma IGF-I increases of 1.5- to 3-fold persisting 9 to 11 days. Estimated half-life was 5.8 to 8.1 days. After multiple doses, mean IGF-I stayed above baseline for up to 28 days, and the trial reported no serious adverse reactions (Teichman et al., 2006).
Pulsatility findings
A separate study measured GH secretion overnight, before and one week after a single injection of CJC-1295 with DAC, in healthy men. GH secretion increased with preserved pulsatility: pulse frequency and magnitude were unaltered. What changed was the trough between pulses, which increased about 7.5-fold, contributing to a 46 percent rise in mean GH and a 45 percent rise in IGF-I. The study put half-life at approximately 8 days and attributed the IGF-I increase mainly to the elevated trough rather than pulse frequency or amplitude (Ionescu and Frohman, 2006).
No comparable published human PK trial for the unconjugated, no-DAC analog was identified in the sources reviewed; its public characterization is concentrated in structural and regulatory documentation rather than dedicated PK studies (FDA Pharmacy Compounding Advisory Committee briefing document, 2024).
| Reported finding | CJC-1295 without DAC | CJC-1295 with DAC |
|---|---|---|
| Albumin binding | None described in the reviewed literature | Covalent, via maleimide to albumin Cys34 |
| Published human half-life | Not established in a dedicated PK trial in the sources reviewed | 5.8 to 8.1 days (Teichman et al., 2006); approximately 8 days (Ionescu and Frohman, 2006) |
| GH pulsatility in cited studies | Not directly studied for this form in the sources reviewed | Pulse frequency and magnitude preserved; trough GH raised about 7.5-fold (Ionescu and Frohman, 2006) |
| Common research pairing | Often studied alongside a GHRP such as ipamorelin or GHRP-6 | Studied on its own in the cited human trials |
Why do researchers pair CJC-1295 without DAC with a GHRP?
GHRH analogs and growth hormone-releasing peptides (GHRPs) act on different receptors. GHRH analogs, including both forms of CJC-1295, bind the GHRH receptor on pituitary somatotrophs. GHRPs such as ipamorelin and GHRP-6 bind the ghrelin receptor, formally the growth hormone secretagogue receptor. The two pathways are studied together because they interact rather than simply adding together.
Ipamorelin
Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2) characterized as a selective GH secretagogue. In profiling with receptor antagonists, ipamorelin released GH through the same GHRP-like receptor as GHRP-6, with comparable potency in rat and pig models, but without significantly raising ACTH or cortisol, unlike GHRP-6 and GHRP-2 in that study (Raun et al., 1998). Because of that selectivity, ipamorelin is one of the GHRPs researchers pair with GHRH-receptor agonists like CJC-1295; see our CJC-1295 (No DAC) and ipamorelin monograph and our CJC-1295 (No DAC) plus ipamorelin lot page.
GHRP-6
GHRP-6's relationship to endogenous GHRH signaling has been tested directly. Using a GHRH receptor antagonist, one study found that blocking endogenous GHRH nearly eliminated the GH response to a GHRP-6 bolus in healthy men, reducing the peak GH rise from a mean of 33.8 to 6.2 micrograms per liter (Pandya et al., 1998). The authors concluded that endogenous GHRH is necessary for most of the GH response to GHRP-6 in humans, a dependency the literature cites as a reason to pair the two rather than studying either alone. See our CJC-1295 (No DAC) and GHRP-6 monograph, our CJC-1295 (No DAC) plus GHRP-6 lot page, and the growth hormone secretagogue comparison.
What does pulsatility mean in this context?
Endogenous GH is released in discrete pulses, separated by low troughs, under the joint control of GHRH and somatostatin, not at a steady rate. The pulsatility study on CJC-1295 with DAC found that a single injection did not collapse this pattern into a flat, continuous elevation: pulses kept their normal frequency and size, while the trough between pulses rose substantially (Ionescu and Frohman, 2006). That distinction, preserved pulse architecture versus an elevated floor, is why researchers studying GHRH-pathway compounds track pulsatility rather than relying on single time-point GH measurements alone.
Regulatory status
Neither CJC-1295 without DAC nor CJC-1295 with DAC is a component of an FDA-approved drug, and there is no United States Pharmacopeia or National Formulary monograph for either substance. In December 2024, the FDA's Pharmacy Compounding Advisory Committee reviewed CJC-1295-related bulk drug substances, including the free base, acetate, and DAC forms, as part of its ongoing evaluation of substances nominated for the 503A bulk drug substances list, noting gaps in publicly available impurity, aggregation, and endotoxin data at the time of review (FDA Pharmacy Compounding Advisory Committee briefing document, 2024). Homegrown Peptides sells CJC-1295 research materials strictly for laboratory research, not for human or animal use.
Handling notes
Both forms ship as lyophilized powder and require the same bench-level care as other research peptides: reconstitution with an appropriate diluent, gentle swirling rather than shaking, and cold storage of both lyophilized and reconstituted material. Because the DAC form depends on an intact maleimide group that has not yet reacted with a thiol, minimizing freeze-thaw cycles and time at room temperature helps preserve that reactive site before use in an experiment.
Frequently asked questions
Is CJC-1295 with DAC the same molecule as CJC-1295 without DAC?
No. Both share the same tetrasubstituted GHRH(1-29) backbone (D-Ala2, Gln8, Ala15, Leu27), but the DAC form adds a maleimidopropionic acid linker at the C-terminus that the no-DAC form lacks. FDA's 2024 review treats them as distinct active moieties.
What does DAC stand for, and what does it bind to?
Drug Affinity Complex: a maleimide group that forms a covalent bond with a free thiol on circulating albumin, at cysteine 34, linking the peptide to the albumin molecule.
What half-life has been reported for CJC-1295 with DAC?
Published studies reported an estimated half-life of 5.8 to 8.1 days (Teichman et al., 2006) and approximately 8 days in a related study (Ionescu and Frohman, 2006). No comparable dedicated half-life study for the no-DAC form was identified in the sources reviewed.
Why is CJC-1295 without DAC often studied alongside ipamorelin or GHRP-6 rather than alone?
GHRH-receptor agonists and GHRPs act on different receptors that appear to interact rather than act independently. Blocking endogenous GHRH nearly abolished the GH response to GHRP-6 in one study (Pandya et al., 1998), an interdependency the literature cites as rationale for studying the two classes together.
Does CJC-1295 with DAC eliminate normal GH pulsatility?
No. The cited study reported that pulse frequency and magnitude were unchanged after a single dose; what increased was the trough level between pulses (Ionescu and Frohman, 2006).
Is CJC-1295 FDA-approved?
No. Neither form is a component of an FDA-approved drug, and as of the FDA's December 2024 review, both remained under evaluation for the 503A bulk drug substances list.
References
- Guillemin R, Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB. Growth hormone-releasing factor from a human pancreatic tumor that caused acromegaly. Science. 1982;218(4572):585-587.
- Rivier J, Spiess J, Thorner M, Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982;300(5889):276-278.
- Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J Clin Invest. 1986;78(4):906-913.
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805.
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797.
- Pandya N, DeMott-Friberg R, Bowers CY, Barkan AL, Jaffe CA. Growth hormone (GH)-releasing peptide-6 requires endogenous hypothalamic GH-releasing hormone for maximal GH stimulation. J Clin Endocrinol Metab. 1998;83(4):1186-1189.
- Raun K, Hansen BS, Johansen NL, Thøgersen H, Madsen K, Ankersen M, Andersen PH. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561.
- U.S. Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting, CJC-1295-Related Bulk Drug Substances. December 4, 2024.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
