CJC-1295 is a synthetic growth-hormone-releasing hormone (GHRH 1-29) analog and GHRH-receptor agonist developed using drug affinity complex (DAC) albumin-binding technology. It exists in two frequently-confused forms: a DAC-bearing 30-residue peptide that covalently binds serum albumin for a multi-day half-life, and a no-DAC counterpart (Modified GRF 1-29) that is short-acting. First characterized by Jetté and colleagues in 2005, it has been studied as a long-acting modulator of the growth hormone/IGF-I axis and is prominently referenced in anti-doping analytical chemistry. This overview summarizes the published scientific literature on its chemistry, mechanism, and research applications.

Background & Discovery

CJC-1295 is a synthetic analog of the biologically active 1-29 fragment of growth-hormone-releasing hormone (GHRH, also called GHRF/GRF). It was developed by the Montreal biotechnology firm ConjuChem (from which the "CJC" designation derives) as part of a program applying the company’s Drug Affinity Complex (DAC) technology to short-lived peptide hormones. The seminal characterization was published by Jetté and colleagues in Endocrinology (2005), who synthesized maleimido derivatives of human GRF(1-29) designed to bond in vivo to circulating serum albumin and screened them for receptor activity and durability; among these, CJC-1295 (DAC:GRF) was identified as a stable, long-lasting GRF-receptor agonist.

The scientific interest in CJC-1295 stems from a central limitation of native GHRH: its plasma half-life is only a few minutes because it is rapidly cleaved by dipeptidyl peptidase-IV (DPP-IV) at the N-terminus and cleared renally. Native GHRH and its early analog sermorelin therefore require frequent administration to sustain any effect on the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis. CJC-1295 was engineered to overcome this through two complementary strategies: point substitutions that harden the peptide against enzymatic degradation, and a bioconjugation handle that tethers the peptide to albumin, dramatically extending its residence time. Human pharmacology studies subsequently reported a terminal half-life measured in days rather than minutes.

In the research-chemical and analytical literature, CJC-1295 exists in two related but distinct forms that are often confused: the DAC-bearing form (CJC-1295 with DAC / DAC:GRF), a 30-residue peptide carrying the reactive maleimidopropionyl-lysine, and the no-DAC form (Modified GRF 1-29), the 29-residue peptide with the same four stabilizing substitutions but without the albumin-binding handle. The DAC form is characterized by an extended, multi-day duration of action, whereas the no-DAC form retains only a short half-life. Although CJC-1295 was investigated clinically for GH-deficiency-related indications and did not proceed to marketing approval, it remains a frequently referenced reference compound in endocrine pharmacology, in long-acting-peptide drug-delivery research, and prominently in anti-doping analytical chemistry, where it is a WADA-prohibited substance (class S2).

Chemical Identity

Structure & Physicochemical Properties

CJC-1295 with DAC is a 30-amino-acid peptide amide (molecular formula C165H269N47O46; average mass ~3647.2 g/mol for the unconjugated species) built on the GHRH(1-29) scaffold. It carries four residue substitutions relative to native GHRH/sermorelin (D-Ala2, Gln8, Ala15, Leu27) plus a C-terminal lysine (Lys30) functionalized on its epsilon-amine with a 3-maleimidopropionyl group. The D-alanine at position 2 blunts N-terminal DPP-IV cleavage, and the internal substitutions reduce susceptibility to other proteolytic and oxidative degradation pathways; the peptide literature describes these modifications as conferring markedly enhanced in-vitro stability, including resistance to DPP-IV. The no-DAC counterpart (Modified GRF 1-29; C152H252N44O42; ~3367.9 g/mol) is the same substituted 29-mer without the maleimidopropionyl-lysine, and consequently lacks the covalent albumin-binding capability that defines the DAC species.

As a highly polar, multiply charged polypeptide, CJC-1295 is water-soluble and is typically supplied as a lyophilized (freeze-dried) powder, frequently as an acetate or trifluoroacetate salt. The defining physicochemical feature of the DAC form is the maleimide group, an electrophilic Michael acceptor that reacts selectively with free thiols. Under physiological conditions this group forms a stable thioether bond with the single reduced cysteine (Cys34) on serum albumin, which is the basis of the compound’s extended half-life. That same reactivity is a practical handling consideration: the maleimide can react with any accessible thiol (including reducing agents or thiol-containing buffers) and is subject to hydrolytic ring-opening over time, so freshly reconstituted, thiol-free preparations are preferred for reproducible chemistry.

Mechanism of Action — as described in the literature

CJC-1295 acts as an agonist at the growth-hormone-releasing hormone receptor (GHRH-R), a class B G-protein-coupled receptor expressed on somatotroph cells of the anterior pituitary. Like native GHRH, binding activates the Gs/adenylate cyclase/cAMP-PKA cascade, stimulating both the synthesis and the pulsatile release of growth hormone. The pituitary-released GH in turn drives hepatic and peripheral production of IGF-I, the principal downstream mediator of many GH actions. In their foundational study, Jetté et al. demonstrated that hGRF(1-29)-albumin bioconjugates retain the ability to activate the GRF receptor and evoke GH secretion in cultured rat anterior pituitary cells, establishing that appending the DAC handle and binding albumin does not abolish receptor engagement.

The distinguishing mechanistic element of the DAC form is its in-vivo bioconjugation to albumin. The Nε-maleimidopropionyl group on Lys30 undergoes a Michael addition with the free thiol of Cys34 on serum albumin, forming a covalent thioether adduct shortly after administration. Because albumin is abundant, long-lived, and largely confined to the circulation, this tethering converts a rapidly cleared small peptide into a slowly eliminated macromolecular species. Jetté and colleagues reported that CJC-1295 remained immunoreactive on the albumin band for more than 24 hours and was detectable in circulation beyond 72 hours in rats, while resisting DPP-IV degradation in vitro. The combined effect of the stabilizing substitutions and albumin anchoring is a duration of action orders of magnitude longer than native GHRH.

Human pharmacology studies translated this into a multi-day pharmacodynamic profile. Teichman et al. reported dose-dependent, sustained elevations of GH and IGF-I following single subcutaneous administration, with an estimated terminal half-life of roughly 5.8 to 8.1 days and IGF-I elevations persisting for many days; repeated administration maintained IGF-I above baseline for weeks. This kinetic behavior reflects the slow turnover of the albumin-bound depot rather than repeated short bursts of receptor activation.

A notable mechanistic subtlety is that continuous GHRH-R stimulation does not flatten the physiological GH rhythm. Ionescu and Frohman found that during sustained stimulation by CJC-1295 in healthy adults, GH continued to be secreted in discrete pulses; pulse frequency and amplitude were essentially unchanged while basal (trough) GH levels rose markedly (about 7.5-fold), and it was this elevation of trough secretion that correlated with the increase in IGF-I. This indicates that hypothalamic somatostatin tone continues to sculpt pulsatility even under a long-acting GHRH agonist, distinguishing GHRH-analog pharmacology from exogenous GH administration, which suppresses endogenous secretion and abolishes pulsatility.

Because CJC-1295 works upstream at the level of the pituitary somatotroph, its action is generally described as depending on a functional GH-secretory apparatus and remaining subject to negative feedback from IGF-I and somatostatin. In genetic models lacking endogenous GHRH, Alba et al. showed that exogenous CJC-1295 can substitute for the missing hypothalamic signal: once-daily administration normalized somatic growth and increased pituitary GH mRNA and total RNA, consistent with trophic stimulation and proliferation of somatotrophs, whereas less frequent dosing was less effective.

Key Published Findings

• Discovery and albumin bioconjugation (in vitro / rat): Jetté et al. synthesized three maleimido derivatives of hGRF(1-29) and bioconjugated them to the Cys34 thiol of human serum albumin. All conjugates showed enhanced in-vitro stability against DPP-IV and remained bioactive in a GH-secretion assay using cultured rat anterior pituitary cells. In rats, CJC-1295 produced roughly a 4-fold increase in GH area-under-the-curve over 2 hours versus unconjugated hGRF(1-29), persisted as an albumin-bound immunoreactive species for >24 hours, and was detectable beyond 72 hours, identifying it as a long-lasting GRF analog.[1]
• Human pharmacokinetics and GH/IGF-I response: In two randomized, placebo-controlled, double-blind ascending-dose trials in healthy adults, Teichman et al. reported that single subcutaneous doses produced dose-dependent increases in mean plasma GH of 2- to 10-fold for 6 days or more and increases in IGF-I of 1.5- to 3-fold sustained for roughly 9-11 days. The estimated terminal half-life was 5.8-8.1 days, and repeated dosing kept mean IGF-I above baseline for up to about 28 days; treatment was reported as well tolerated in the studied dose range.[2]
• Preservation of pulsatile GH secretion (human): Ionescu and Frohman found that continuous stimulation by CJC-1295 in healthy adults preserved the pulsatile pattern of GH release: pulse frequency and amplitude were essentially unchanged while basal (trough) GH levels rose markedly (~7.5-fold). Overall GH secretion increased ~46% and IGF-I ~45%, and the rise in trough GH, rather than any change in pulse characteristics, appeared responsible for the increase in IGF-I.[3]
• Rescue of growth in a GHRH-deficient model (mouse): In GHRH-knockout mice, Alba et al. showed that once-daily administration of CJC-1295 normalized body weight, length, and body composition, whereas the same dose given every 48 or 72 hours was less effective. Treatment increased total pituitary RNA and GH mRNA, consistent with proliferation of somatotroph cells and a trophic effect of sustained GHRH-receptor signaling.[4]
• Analytical detectability and albumin conjugation: Analytical-chemistry studies highlight that the DAC form’s maleimidopropionic acid group covalently links the peptide to free thiols on plasma proteins, effectively converting it into a macromolecular albumin adduct that evades conventional top-down/intact peptide mass-spectrometry screening. Knoop et al. developed an immunoaffinity-purification LC-HRMS/MS method targeting multiple GHRHs (including CJC-1293 and CJC-1295) in human plasma, and Timms et al. developed an immuno-PCR assay detecting the CJC-1295-protein conjugate in equine plasma down to sub-pg/mL levels.[6]

Research Applications

• Investigated as a pharmacological tool for probing GHRH-receptor signaling and somatotroph biology in cultured pituitary cells and rodent models.
• Studied as a modulator of the GH/IGF-I axis to characterize dose-response, duration of action, and feedback regulation in animal and human pharmacology.
• Examined as a model system for albumin-binding (Drug Affinity Complex) technology and long-acting peptide drug-delivery engineering.
• Used in genetic models of GH/GHRH deficiency (e.g., GHRH-knockout mice) to test whether an exogenous long-acting GHRH agonist can restore somatic growth and body composition.
• Investigated in studies of GH secretory dynamics and pulsatility to understand how a sustained GHRH signal interacts with somatostatin tone.
• Employed in comparative peptide-pharmacology research alongside sermorelin, tesamorelin, CJC-1293, and ghrelin-receptor agonists to contrast half-life and mechanism.
• Used extensively in anti-doping analytical method development for human plasma (immunoaffinity LC-HRMS/MS) given its WADA-prohibited status.
• Applied in veterinary/equine doping-control research, including immuno-PCR and LC-MS/MS confirmation of GHRH analogs in horse plasma.
• Referenced in forensic/quality analyses identifying GHRH peptides in unknown or gray-market pharmaceutical preparations.
• Studied for peptide-stability and protease-resistance (DPP-IV) structure-activity relationships in GHRH analog design.

Related & Comparator Compounds

CJC-1295 sits within the GHRH-agonist class and is most directly compared with sermorelin (native GHRH 1-29), tesamorelin (a stabilized GHRH(1-44) analog), and CJC-1293 (a closely related DAC-conjugated GRF analog frequently co-listed in anti-doping assays). Its own no-DAC counterpart, Modified GRF(1-29), shares the four stabilizing substitutions but omits the maleimidopropionyl-lysine handle, so the literature distinguishes the two chiefly by duration of action: the DAC form exhibits a multi-day half-life via covalent albumin binding, whereas the no-DAC form retains only a short half-life. A separate mechanistic category is the growth-hormone secretagogues / ghrelin-receptor (GHS-R) agonists, such as ipamorelin, GHRP-2, GHRP-6, and hexarelin, which stimulate GH through a distinct receptor and are commonly studied alongside GHRH analogs because the two mechanisms act on different receptors of the somatotroph. Anti-doping and structural chemistry papers emphasize that, unlike small-molecule secretagogues, CJC-1295’s albumin conjugation makes it analytically unusual because the circulating species is effectively a peptide-protein adduct.

Handling, Reconstitution & Storage

In the research literature and on supplier certificates of analysis, CJC-1295 is typically described as a lyophilized powder that should be stored desiccated and protected from light, commonly at -20°C (or colder) for long-term storage, with short-term stability at refrigerated temperatures. For laboratory use it is generally reconstituted in sterile or bacteriostatic water (or a suitable buffer), then aliquoted to minimize repeated freeze-thaw cycles, which can degrade peptide integrity; reconstituted solutions are usually kept refrigerated and used within a limited window. For the DAC form specifically, the electrophilic maleimide handle reacts with free thiols and is subject to slow hydrolysis, so thiol-containing reducing agents and reactive buffers are typically avoided when the intact reactive species is required. All handling described here is strictly in a laboratory research context for research-use-only material; this information is not a dosing or administration guide and no human or veterinary use is implied.

Analytical & Quality Considerations

Identity and purity of CJC-1295 are typically established by reversed-phase HPLC (purity commonly specified at ≥95-98%) combined with mass spectrometry (ESI-MS or MALDI-TOF) to confirm the average/monoisotopic mass against the expected ~3647.2 g/mol for the DAC form or ~3367.9 g/mol for the no-DAC Modified GRF(1-29), which also provides the clearest way to discriminate the two frequently-confused species. Orthogonal characterization can include tandem MS/MS sequencing to verify the amino-acid sequence and the presence (or absence) of the maleimidopropionyl-lysine, amino-acid analysis or nitrogen determination for true peptide content, Karl Fischer titration for water, and ion chromatography for counterion (acetate/TFA) content; endotoxin and residual-solvent testing are relevant for research-grade material. Because database entries and vendor listings routinely conflate the DAC and no-DAC forms (including inconsistent CAS-to-formula mappings), independent third-party COAs with the raw HPLC chromatogram and mass spectrum are important for confirming which species is actually present and at what purity. Analytical papers further note that the DAC form’s covalent conjugation to albumin Cys34 means the intact reactive peptide is difficult to detect once in a biological matrix, which is why specialized immunoaffinity LC-HRMS/MS and immuno-PCR approaches were developed.

Frequently Asked Research Questions

Q. What is the difference between CJC-1295 with DAC and CJC-1295 without DAC?
A. Both are GHRH(1-29) analogs carrying the same four stabilizing substitutions (D-Ala2, Gln8, Ala15, Leu27). The with-DAC form adds a C-terminal lysine bearing a maleimidopropionyl group (the Drug Affinity Complex handle), a 30-residue peptide (C165H269N47O46, ~3647 g/mol) that covalently binds albumin for a multi-day half-life. The no-DAC form, Modified GRF(1-29), is the 29-residue peptide without that handle (C152H252N44O42, ~3368 g/mol) and is characterized in the literature as short-acting.

Q. What does ‘DAC’ mean and how does it extend the half-life?
A. DAC stands for Drug Affinity Complex. In CJC-1295, a maleimide group on the C-terminal lysine reacts (via Michael addition) with the free thiol of cysteine-34 on serum albumin, forming a stable covalent thioether adduct. Tethering the small peptide to abundant, long-lived albumin slows its clearance, and published human pharmacology reports an estimated terminal half-life of roughly 5.8-8.1 days.

Q. How does CJC-1295 differ from sermorelin and tesamorelin?
A. All three are GHRH-receptor agonists. Sermorelin is native GHRH(1-29) with a short half-life; tesamorelin is a stabilized GHRH(1-44) analog. CJC-1295 uses residue substitutions plus (in the DAC form) covalent albumin binding to achieve a duration of action measured in days rather than minutes, which is the defining pharmacokinetic distinction reported in the literature.

Q. Why is CJC-1295 studied alongside ghrelin mimetics such as ipamorelin?
A. CJC-1295 is a GHRH-receptor agonist, whereas ipamorelin and the GHRPs act on the separate ghrelin/GHS receptor. Because they engage different receptors on the same somatotroph cells, researchers frequently examine them in parallel to compare and contrast the two distinct routes of stimulating growth hormone secretion.

Q. Is CJC-1295 an approved medicine?
A. No. CJC-1295 was investigated in early clinical pharmacology studies but did not proceed to marketing approval. It is handled as a research-use-only reference compound and is prohibited in sport under the World Anti-Doping Agency’s S2 category. Nothing here should be read as medical guidance or a claim of benefit.

Q. Why is CJC-1295 hard to detect in doping-control samples?
A. In blood, the DAC form’s maleimide group covalently attaches the peptide to plasma proteins such as albumin, so the circulating molecule is effectively a large protein adduct rather than a free peptide. This defeats conventional intact-peptide mass-spectrometry screening, which is why specialized immunoaffinity LC-HRMS/MS (human) and immuno-PCR (equine) methods were developed.

Peer-Reviewed References

1. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005. PubMed →
2. 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. Journal of Clinical Endocrinology & Metabolism. 2006. PubMed →
3. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology & Metabolism. 2006. PubMed →
4. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American Journal of Physiology – Endocrinology and Metabolism. 2006. PubMed →
5. Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Testing and Analysis. 2010. PubMed →
6. Knoop A, Thomas A, Fichant E, Delahaut P, Schänzer W, Thevis M. Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS. Analytical and Bioanalytical Chemistry. 2016. PubMed →
7. Timms M, Ganio K, Forbes G, Bailey S, Steel R. An immuno polymerase chain reaction screen for the detection of CJC-1295 and other growth-hormone-releasing hormone analogs in equine plasma. Drug Testing and Analysis. 2019. PubMed →

For laboratory and research use only. Not for human or veterinary use, diagnosis, or treatment. This overview summarizes published scientific literature for informational and educational purposes and is not medical advice; no claims are made regarding safety or efficacy in humans.

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