CJC-1295 with DAC 5mg

Product status information

Chemical reagent intended exclusively for laboratory tests (Research Use Only). It is not a medicinal product, dietary supplement or food. It is not intended for use on humans or animals. Sales only to registered research units and laboratories.

Regulatory framework – long-acting GHRH analogue with DAC

CJC-1295 with DAC 5 mg is research reagent from the Endogenic line in the form of a lyophilized product in a vial, containing a modified growth hormone releasing hormone analogue – GHRH(1-29) fragment with attached drug affinity complex (DAC), which binds irreversibly to plasma albumin. This is a variant with DAC — with a very long half-life (of the order of days), pharmacokinetically different from the variant without DAC (Mod-GRF 1-29).

The molecule belongs to the class of growth hormone secretagogues, which WADA lists in section S2 of the prohibited list (peptide hormones, growth factors and mimetics) – permanently prohibited substance, both in and out of competition. Communication suggesting human use to increase growth hormone, IGF-1 levels, accelerate recovery or body composition is contrary to the Research Use Only framework and is unacceptable.

Growth hormone does not flow from the pituitary gland in a flat, constant stream – the somatotropic cell releases GH impulses, in pulses of a specific amplitude and frequency, regulated by opposing signals from the hypothalamus. GHRH (growth hormone releasing hormone) tells the pituitary to “release”, somatostatin says “hold”. Endogenous GHRH, however, has an important limitation as a research tool: it is a peptide with a very short half-life — minutes — because it is quickly broken down by plasma proteases, primarily dipeptidyl peptidase-4 (DPP-4). The entire story of CJC-1295 stems from this limitation.

CJC-1295 is an attempt to answer one question in the pharmacology of the somatotropic axis: how to maintain the stimulation of the GHRH receptor for days, not minutes, while maintaining the physiological, pulsatile architecture of GH secretion? The answer developed by ConjuChem was a two-step modification of the GHRH(1-29) fragment: first, amino acid substitutions protecting the peptide against enzymatic degradation, and then the addition of drug affinity complex (DAC) — a reactive maleimide-propionic linker, which, once introduced into the circulation, binds covalently and irreversibly to plasma albumin.

Albumin now serves as a reservoir for the molecule, protecting it from renal filtration and proteolysis – hence the multi-day half-life that distinguishes this variant from all classic GHRH analogues. This reagent is supplied as 5 mg lyophilisate in a vial, for reconstitution with bacteriostatic water in laboratory conditions. The freeze-dried form ensures stability of the peptide before dissolution and allows researchers to prepare working concentrations tailored to the experimental design. Purity verified by HPLC ≥98%, identity confirmed by Q-TOF mass spectrometry, COA available for each batch.

It remains the reference point for comparative studies on the GHRH arm without prolonged albumin retention CJC-1295 without DAC with a short half-life, and the complementary arm of ghrelin represents Ipamorelin from the GHRP class.

To understand what a long-acting GHRH analogue is, you need to see that the pituitary gland receives the “GH secretion” signal through more than one channel. The somatotropic cell of the anterior pituitary has at least two separate receptors on its surface that stimulate the release of growth hormone: GHRH receptor and growth hormone secretion receptor type 1a (GHS-R1a), i.e. ghrelin receptor.

These are two different proteins, two different intracellular cascades and two different physiological signals – which converge on the same end result, the release of GH from secretory granules. GHRH receptor is a receptor coupled to the Gs protein.

Its stimulation increases intracellular cAMP, activates the PKA kinase-dependent pathway and leads to the release of growth hormone. Physiologically, GHRH is primarily responsible for amplitude GH pulse – for how high a single hormone release is. This is the channel on which CJC-1295 is based. Ghrelin receptor (GHS-R1a) is a Gq protein-coupled receptor; its arousal affects frequency and pulsatility GH secretion and suppresses somatostatin – this is the channel on which GHRP class peptides (Ipamorelin, GHRP-2) are based. The pulsatile nature of GH secretion is the main physiological detail here.

Unlike exogenous, recombinant growth hormone, which floods the circulation with a flat, non-physiological concentration, GHRH analogues stimulate own pituitary to release GH in a way that preserves the pulsatile signal architecture – involving the somatostatin feedback loop. What is important for CJC-1295 with DAC: even with long-term, sustained exposure to the GHRH analogue, GH secretion remains pulsating — studies have shown that a constant increase in the concentration of the analogue does not abolish pulsatility, but maintains a higher basic level at which physiological pulses are superimposed (Ionescu, Frohman 2006). The pharmacology of growth hormone secretagogues includes two large classes of tools:

• GHRH analogues — mimic the endogenous GH-releasing hormone, stimulate the GHRH receptor, increase the pulse amplitude (CJC-1295, sermorelin, tesamorelin)
• GH-releasing peptides (GHRP) and ghrelin mimetics — stimulate the GHS-R1a ghrelin receptor, increase the pulse rate and suppress somatostatin (Ipamorelin, GHRP-2, GHRP-6, hexarelin)

The CJC-1295 with DAC occupies a special position in the first class: it is the longest-acting GHRH analogue characterized in the literature, which makes it a model tool for studying how sustained, multi-day stimulation of the GHRH receptor affects the GH/IGF-1 axis – as opposed to short-term, pulsed stimulation provided by analogues without DAC. This entire class of tools—from GHRH analogues to ghrelin mimetics—falls into the category growth hormone-increasing peptides.

Chemically, CJC-1295 with DAC is a modified 29-amino acid peptide with an attached albumin-binding linker.

• Common name: CJC-1295 with DAC, DAC:GRF
• Descriptive name: modified GHRH(1-29) analogue with Drug Affinity Complex
• Synonyms: CJC-1295 DAC, DAC:GRF, drug affinity complex GRF, long-acting GHRH analogue
• CAS number: 863288-34-0 (to be verified in the batch COA)
• Molar mass: ~3647 g/mol (variant with DAC) (to be verified in the batch COA)
• Chemical class: modified growth hormone releasing hormone analogue GHRH(1-29); core with stabilizing substitutions (Asp³, Ala⁸, Arg²⁹, Leu²⁷) plus a reactive maleimide-propionic linker that irreversibly binds plasma albumin
• Delivered form: 5 mg lyophilisate in a vial, for reconstitution with bacteriostatic water; pharmaceutical grade ≥98% HPLC

Origin: CJC-1295 is derived from GHRH(1-29) — the shortest, fully biologically active fragment of human growth hormone releasing hormone (also known as sermorelin). Endogenous GHRH(1-29) is effective but unstable – plasma proteases, particularly DPP-4, break it down within minutes. The ConjuChem team has developed two levels of modification. The first is amino acid substitutions (Asp³, Ala⁸, Arg²⁹, Leu²⁷) that protect the peptide from enzymatic cleavage – this stabilized core is itself a variant without DAC (Mod-GRF 1-29).

The second step is joining drug affinity complex (DAC): a reactive maleimide-propionic group which, when introduced into the circulation, forms an irreversible covalent bond with the cysteine-34 residue of serum albumin. An albumin–GHRH bioconjugate is formed, in which albumin protects the analog from renal filtration and degradation, extending the half-life from minutes to days (Jetté et al. 2005; Teichman et al. 2006).

💡 SCIENTIFIC PERSPECTIVE Data regarding CJC-1295 with DAC come mainly from early Phase I clinical trials conducted by ConjuChem (Teichman et al. 2006), analyzes of GH secretion pulsatility with maintained stimulation (Ionescu, Frohman 2006), and characterization of albumin bioconjugate technology in rat models (Jetté et al. 2005). The mechanisms described – prolonged GH/IGF-1 stimulation, albumin retention, preserved pulsatility – are of a reference nature and describe the profile of the molecule in the literature, not the expected result of work with the RUO reagent.

The ConjuChem clinical program did not lead to drug registration, and the PK/PD profile with multi-day exposure in humans remains insufficiently characterized. Extrapolation to any human use is inconsistent with the Research Use Only framework.

The operation of the CJC-1295 with DAC is based on the combination of two elements: classic GHRH receptor agonism and extended albumin retention technology (DAC). This distinction is important – the receptor mechanism is the same as endogenous GHRH, but the pharmacokinetics are fundamentally different.

GHRH receptor agonism – pulse amplitude. Activation of the GHRH receptor (Gs-coupled protein) on the somatotropic cell increases intracellular cAMP and triggers the PKA kinase-dependent pathway. The effect is increasing pulse amplitude — a single release of growth hormone becomes higher. In a working analogy: The CJC-1295 regulates the “volume” of the GH signal.

The core of the molecule is a fragment of GHRH(1-29), so at the receptor level the analogue mimics the endogenous hormone – the difference is not in What does with the receptor, but How long is able to do this.

DAC technology – irreversible binding of albumin. The heart of the molecule is a reactive maleimide-propionic linker. After reconstitution and introduction into an albumin-containing medium, the maleimide group reacts with the free cysteine-34 thiol group of serum albumin, forming permanent, covalent thioether bond. The resulting bioconjugate circulates bound to albumin, a protein with its own multi-day half-life.

Albumin acts as a reservoir: it protects the GHRH analog from glomerular filtration in the kidneys and from proteolytic degradation, while keeping it in circulation and slowly releasing the active form. It is DAC technology that translates the half-life from minutes to 6–8 days (Jetté et al. 2005).

Stabilizing modifications – protection against proteases. Independent of DAC, the peptide core itself contains substitutions (Asp³, Ala⁸, Arg²⁹, Leu²⁷) that protect the analogue from cleavage by dipeptidyl peptidase-4 (DPP-4) and other plasma proteases. Endogenous GHRH(1-29) is rapidly inactivated at the Tyr¹-Ala² bond, and substitution at position 8 (and the others) removes this sensitive site.

These modifications increase the stability of the peptide before albumin retention will still come into play.

Multi-day GH stimulation and secondary increase in IGF-1. The combination of the above elements gives a profile unique among GHRH analogues: sustained, multi-day stimulation of the GHRH receptor. In a phase I study (Teichman et al. 2006), a single exposure to CJC-1295 with DAC elevated GH concentrations for many days and led to sustained secondary increase in IGF-1 — a marker reflecting the hepatic response to prolonged GH signaling.

Importantly, despite the constant, increased concentration of the analogue, GH secretion remained pulsating (Ionescu, Frohman 2006) – prolonged exposure to GHRH maintains a higher basal level rather than abolishing the physiological rhythm of pulses.

Synergy with GHRP class peptides. In research protocols, a GHRH analogue is often combined with a ghrelin mimetic (Ipamorelin, GHRP-2) – because both arms act through different receptors and different intracellular cascades. GHRH (CJC-1295) provides the Gs/cAMP signal and increases the amplitude; GHRP stimulates the Gq ghrelin receptor, increases the frequency and suppresses somatostatin.

Because the ghrelin arm abolishes somatostatin inhibition and enhances the response to GHRH, simultaneous stimulation of both pathways produces an effect in the models. greater than the sum of individual actions — this is a classic research pair of GHRH + GHRP on the physiology of the somatotropic axis, also available as a ready-made stack Ipamorelin + CJC-1295.

IMPORTANT DISTINCTION – DAC vs. non-DAC variant

CJC-1295 is in the research market in… two structural variants with fundamentally different pharmacokinetics, which must not be confused:

• CJC-1295 with DAC (this reagent, DAC:GRF) – GHRH(1-29) core with an attached albumin affinity complex (maleimide-propionic linker). Binds irreversibly to plasma albumin → half-life days (~6–8 days) → maintained, multi-day GH/IGF-1 stimulation.
• CJC-1295 without DAC (also known as Mod-GRF 1-29 or modified GRF 1-29) – the same stabilized GHRH(1-29) core, but without albumin complex. Half-life in the order of minutes (~30 min) → short, pulsed stimulation similar to the physiological GHRH signal.

The difference is fundamental for the design of the experiment: the time profile of GH stimulation of the DAC variant (long, sustained, multi-day) and without DAC (short, pulsed) are two different pharmacokinetic models. The presence of DAC in a given batch must be confirmed in the COA — is the specification that the researcher verifies before planning the protocol.

The only binding signal of variant identity is the molecular weight confirmed by mass spectrometry (variant with DAC ~3647 g/mol vs. ~3367 g/mol variant without DAC) – the trade name is not sufficient. This distinction refers to the profile of the molecule in the literature and does not imply application to humans.

CJC-1295 with DAC as an RUO reagent is used where the subject of the study is sustained, multi-day stimulation of the GHRH receptor and its impact on the GH/IGF-1 axis – as opposed to short-term, pulsed stimulation. In vivo models (rat, mouse, pig as a model species for GH physiology) and in vitro models (isolated somatotropic pituitary cells, cell lines expressing the GHRH receptor) are conducted on the mechanism, kinetics and technology of albumin retention. Specific research directions include:

• Pharmacokinetics of DAC technology — comparison of the time profile of GH stimulation of the variant with DAC (prolonged albumin retention, days) and without DAC (short exposure, minutes) in in vivo models; studies of the structure-time of action relationship and the kinetics of albumin bioconjugate formation
• Maintained stimulation of the GH/IGF-1 axis — measurements of GH and the secondary marker IGF-1 as a response to multi-day stimulation of the GHRH receptor; studies on hepatic IGF-1 production in response to continuous vs. pulsed GH signal
• Pulsatility with continuous stimulation — studies on how the maintained, elevated concentration of the GHRH analogue affects the amplitude and frequency of GH pulses; verification whether the pulsatility of secretion is maintained despite constant exposure to the agonist (model Ionescu, Frohman 2006)
• GHRH + GHRP synergy — measurements of GH release from isolated pituitary cells when stimulated separately with a GHRH analogue, separately with a ghrelin mimetic and both simultaneously; quantitative characterization of additive vs. synergistic effect
• Somatostatin axis — the role of the somatostatin feedback loop in shaping the GH response to sustained GHRH stimulation; Pulse amplitude regulation studies
• GH deficiency models — assessment of the potential of somatotropic signaling in models of GH axis hypofunction; response profile to long-acting versus short-acting GHRH analogue (Alba et al. 2006)

CJC-1295 with DAC 5 mg is RUO research reagent from the Endogenic line – lyophilisate in a vial containing the longest-acting GHRH analogue characterized in the literature. The core of the molecule is a fragment of GHRH(1-29) with stabilizing substitutions (Asp³, Ala⁸, Arg²⁹, Leu²⁷) protecting against DPP-4, and the central element is drug affinity complex (DAC) — maleimide-propionic linker, which irreversibly binds plasma albumin and extends the half-life from minutes to days (~6–8 days).

The receptor mechanism is classic for GHRH: GHRH receptor agonism (Gs/cAMP) increases amplitude growth hormone pulse, and multi-day retention maintains GH stimulation and a secondary increase in IGF-1 – while maintaining the physiological pulsatility of secretion (Teichman et al. 2006; Ionescu, Frohman 2006). The most important distinction: variant with DAC (long T½, days) against the variant without DAC (Mod-GRF 1-29, short T½, minutes) – The presence of DAC is confirmed by the mass of MS in the batch COA. Lyophilized form 5 mg in a vial, reconstitution with bacteriostatic water, HPLC purity ≥98%, MS Q-TOF, COA for each batch.

Regulatory Status – Research Use Only; lack of registration as a medicine; WADA: Section S2, Permanent Prohibited Substance. The guide discusses the broader context of the use of growth hormone secretagogues in bodybuilding sports peptides in bodybuilding, and an oral alternative that stimulates the GH axis through the ghrelin receptor is described in the article MK-677 growth hormone in tablets.

1. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analogue of GH-releasing hormone, in healthy adults. PubMed
2. Ionescu M, Frohman LA (2006). Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. PubMed
3. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, et al. (2005). 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 analogue. PubMed
4. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R (2006). Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. PubMed
5. Sigalos JT, Pastuszak AW (2018). The safety and efficacy of growth hormone secretagogues. PubMed