CJC-1295 DAC Research, Specifications & Scientific Information

CJC-1295 DAC is a synthetic 30-residue analogue of human growth hormone-releasing hormone carrying a maleimidopropionamide group that bonds covalently to serum albumin, giving it a plasma half-life measured in days. It is not approved by the FDA for any indication; clinical development reached phase 2 and stopped.

Category: GHRH analogues and GH secretagogues

Introduction

CJC-1295 is the compound that the name properly belongs to: a growth hormone-releasing hormone analogue that does not merely resist the enzyme that clears the native hormone but attaches itself to a circulating protein so that it is not cleared at all on the usual timescale. A maleimidopropionamide group on a C-terminal lysine reacts with the free thiol on cysteine 34 of serum albumin, and what circulates afterwards is a peptide-albumin conjugate [3]. The reported plasma half-life in healthy adults is measured in days rather than minutes [4].

That is a genuine piece of pharmaceutical chemistry, and CJC-1295 has a real, if short, clinical record: two early-phase trials in healthy adults, a pulsatility study, a proteomic study, and one registered phase 2 trial that was terminated. It has no approval, and development did not continue. This page sets out what was measured, in whom, and where the evidence stops.

What Is CJC-1295 DAC?

CJC-1295 is a synthetic 30-residue peptide developed by ConjuChem Inc. Residues 1 to 29 are a tetrasubstituted form of human growth hormone-releasing hormone 1-29; residue 30 is an added lysine carrying the conjugating group.

The design problem it addresses is old and specific. Growth hormone-releasing hormone is cleared from plasma within minutes, which is what has always limited its therapeutic use [4]. Two independent countermeasures are built into this molecule. The substitutions on the backbone — D-alanine at position 2 above all — block the enzymatic cleavage that starts the clearance. The conjugating group then ties the resulting peptide to albumin, a protein whose own half-life is roughly three weeks.

"DAC" stands for drug affinity complex, the commercial name for that albumin-binding chemistry. The abbreviation matters because the same substituted 29-residue backbone is sold separately, without the conjugating group, as CJC-1295 no DAC. Analytical laboratories treat the two as distinct analytes with distinct metabolites [9], and so should anyone reading a figure attributed to "CJC-1295".

CJC-1295 DAC Specifications

Compound name
CJC-1295 DAC
Full chemical name
Not publicly characterised
Aliases
CJC-1295, CJC-1295 with DAC, CJC-1295 with drug affinity complex, DAC:GRF, tetrasubstituted hGRF(1-29) maleimidopropionamide conjugate
Development code
CJC-1295
CAS number
446262-90-4
PubChem CID
91971820
UNII
62RC32V9N7
Compound type
Synthetic modified peptide
Peptide family
Glucagon / secretin peptide superfamily (growth hormone-releasing hormone analogues)
Amino acid sequence
YaDAIFTQSYRKVLAQLSARKLLQDILSRK
Sequence length
30 residues
Molecular formula
C165H269N47O46
Molecular weight
3647.2 g/mol
Primary target
Growth hormone-releasing hormone receptor (GHRHR)
Secondary targets
Not publicly characterised
Receptor family
Class B1 (secretin-like) G protein-coupled receptors
Agonist / antagonist status
Agonist at the GHRH receptor

The chain above is the 30-residue sequence recorded for CJC-1295 in the FDA/NCATS Global Substance Registration System under UNII 62RC32V9N7, written in single-letter code with a lower-case letter at position 2 to mark D-alanine. The register records one structural modification on that chain: an amino acid substitution at lysine 30 with the maleimidopropionamide derivative that gives the molecule its albumin-binding behaviour, so the single-letter string is not the complete covalent structure. Residues 1 to 29 are a tetrasubstituted form of human growth hormone-releasing hormone 1-29 — D-alanine at 2, glutamine at 8, alanine at 15 and leucine at 27 relative to the sermorelin sequence — and residue 30 is the added lysine that carries the conjugating group. The register also carries CAS registry number 446262-90-4 and PubChem compound identifier 91971820, whose molecular formula and mass agree with the values shown. A different registry number appears in some commercial listings for this material; the number published here is the one the register carries. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does CJC-1295 DAC Work?

The receptor is the growth hormone-releasing hormone receptor, cloned from human anterior pituitary and characterised there as a G protein-coupled receptor that signals through Gs and cyclic AMP [2]. It belongs to the class B1, or secretin-like, family — the same structural class as the receptors for glucagon, GLP-1 and secretin. Activation on a somatotroph leads to growth hormone release; circulating growth hormone in turn drives hepatic production of insulin-like growth factor 1, which is why both are measured in every study of this compound.

Nothing about the conjugation changes which receptor is engaged. What it changes is for how long. A GHRH receptor agonist with a half-life of minutes produces a transient pulse; one with a half-life of days produces something closer to continuous stimulation, and the pharmacological question that follows — whether continuous stimulation of a normally pulsatile axis flattens that pulsatility — was examined directly in human study and is described below.

CJC-1295 DAC Mechanism of Action

In vitro research

The clearance problem was defined before the molecule was. Plasma degradation of growth hormone-releasing hormone proceeds primarily by dipeptidylpeptidase IV cleavage at the 2-3 amino acid bond; the native 44-residue hormone and the shortened 1-32 and 1-29 amides are all rapidly cleaved at that site, and a D-amino acid at position 1 or 2 prevents the hydrolysis [1]. That single finding is the reason position 2 of this molecule is D-alanine.

The conjugation chemistry was characterised in the study that named the compound. Three maleimido derivatives of hGRF(1-29) were synthesised and bioconjugated to human serum albumin ex vivo. All three conjugates showed enhanced in vitro stability against dipeptidylpeptidase IV, and all three were bioactive in a growth hormone secretion assay in cultured rat anterior pituitary cells — the conjugate is not a prodrug that has to be released to work [3].

The in vitro metabolism of the molecule has since been worked out for a different reason. A 2021 study investigated the in vitro metabolism of four of the larger GHRH synthetic analogues — sermorelin, tesamorelin, CJC-1295 and CJC-1295 with drug affinity complex — identified nineteen major metabolites, synthesised and characterised them in house, and used them as reference materials to build a liquid chromatography-tandem mass spectrometry method with limits of detection generally at or below 1 ng/ml [9].

What Is CJC-1295 DAC Being Researched For?

Registered and published research on CJC-1295 has covered, in order of how far each progressed:

  • Pharmacokinetics and the growth hormone / IGF-1 axis in healthy adults — two randomised, placebo-controlled, double-blind early-phase trials [4].
  • Growth hormone secretion patterns under continuous receptor stimulation — an overnight sampling study in healthy men [6].
  • Serum biomarkers of growth hormone action — a proteomic study in healthy young adult men [7].
  • HIV-associated visceral obesity — a registered phase 2 trial, terminated [10].
  • Growth and body composition in a genetic model of GHRH deficiency — mouse work [5].
  • Detection in biological matrices — analytical and anti-doping chemistry [8, 9].

Each of the human items above is research into a pharmaceutical product candidate, conducted by or for its sponsor under a protocol. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on CJC-1295 DAC

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Ascending-amount trials in healthy adults

Population. Healthy participants aged 21 to 61, studied at two investigational sites [4].

Endpoint and duration. Two randomised, placebo-controlled, double-blind ascending-amount trials of 28 and 49 days. The compound or placebo was administered subcutaneously — in one of four ascending single amounts in the first study, and in two or three weekly or biweekly administrations in the second. Main outcome measures were peak concentrations and area under the curve for growth hormone and IGF-1, with standard pharmacokinetic parameters for the compound itself [4].

Result. After a single administration, mean plasma growth hormone concentrations rose two- to tenfold for six days or more, and mean plasma IGF-1 concentrations rose 1.5- to threefold for nine to eleven days; both increases graded with the amount administered. The estimated half-life of the compound was 5.8 to 8.1 days. After repeated administration, mean IGF-1 remained above baseline for up to 28 days [4].

Adverse events. No serious adverse reactions were reported. The authors described the compound as relatively well tolerated, particularly at 30 and 60 µg/kg [4].

Limitations. Early-phase trials in healthy volunteers lasting 28 and 49 days, designed to characterise pharmacokinetics and safety rather than any clinical outcome.

Growth hormone pulsatility in healthy men

Population. Healthy men aged 20 to 40 [6].

Endpoint and duration. Growth hormone secretion patterns assessed by blood sampling every 20 minutes across an overnight 12-hour period, before and one week after a single administration of 60 or 90 µg/kg [6].

Result. Overall growth hormone secretion increased with pulsatility preserved: the frequency and magnitude of secretory pulses were unaltered, while basal trough concentrations rose 7.5-fold (p < 0.0001), mean concentrations rose 46% (p < 0.01) and IGF-1 rose 45% (p < 0.001). No significant difference was observed between the two amounts administered, and the IGF-1 increases did not correlate with any parameter of growth hormone secretion [6].

Limitations. A small mechanistic study in healthy young men, with a single overnight sampling window one week after one administration.

Serum protein profile in healthy adults

Population. Eleven healthy young adult men [7].

Endpoint and duration. Serum collected before and one week after a single administration, analysed by two-dimensional gel electrophoresis with mass spectrometric identification of changed spots [7].

Result. Two spots decreased in intensity and were identified as an apolipoprotein A1 isoform and a transthyretin isoform; three increased and were identified as beta-haemoglobin, a C-terminal fragment of albumin, and a mixture of an immunoglobulin fragment with another C-terminal albumin fragment. A linear relationship was found between the immunoglobulin-and-albumin-fragment spot and IGF-1 concentrations [7].

Limitations. Eleven participants, one timepoint, and a method that identifies candidate biomarkers rather than establishing them. The authors state that the mechanisms linking these proteins to growth hormone and IGF-1 activity remain to be clarified.

Preclinical Research on CJC-1295 DAC

Animal research

The rat work reported alongside the compound's identification is what established the conjugation behaviour in a living animal. Administered subcutaneously to normal male Sprague Dawley rats, the maleimido derivatives each produced an acute rise in plasma growth hormone; the best of them, CJC-1295, gave a fourfold increase in growth hormone area under the curve over two hours compared with hGRF(1-29) and was still present in plasma beyond 72 hours. Western blot analysis of plasma from an injected rat showed immunoreactive compound on the band corresponding to serum albumin from 15 minutes onward, still in circulation beyond 24 hours [3].

A genetic model addressed a different question: whether a long-acting analogue can substitute for the absent hormone. Mice with growth hormone-releasing hormone gene ablation had previously failed to normalise growth even with twice-daily injections of a short-acting analogue. Three groups of one-week-old knockout mice were treated for five weeks with 2 µg of CJC-1295 at intervals of 24, 48 and 72 hours, against placebo-treated knockout mice and heterozygous controls. Animals treated every 24 hours reached normal body weight and length; those treated every 48 or 72 hours exceeded placebo without full normalisation. Femur and tibia length were normal in the 24- and 48-hour groups, relative lean mass and subcutaneous fat mass were normal in all treated groups, and total pituitary RNA and growth hormone mRNA increased, with immunohistochemistry consistent with somatotroph proliferation [5].

A knockout mouse is a model of complete hormone absence, which is not the condition of a normal animal or a normal person. Findings described in this section were observed in animals, and nothing in them establishes anything about humans.

Other Areas of CJC-1295 DAC Research

In vitro research

The most active recent literature on this compound is analytical, and the conjugation that makes it long-lasting is precisely what makes it hard to find. Conjugated CJC-1295 is difficult to detect in blood by mass spectrometry because of its low abundance, its high molecular weight once bound, and its conjugation to a range of different protein substrates. A 2019 method addressed this in equine plasma by immuno-affinity capture followed by tryptic digestion and liquid chromatography-tandem mass spectrometry, identifying the compound down to 180 pg/mL in 1 mL of plasma [8].

The broader review of growth hormone-releasing hormone analogue detection notes that administration of these analogues is prohibited in sport, that use is known from admissions and intelligence, and that they had not been found in anti-doping samples by accredited laboratories — attributed to low urinary concentrations and limited knowledge of the metabolism of unapproved analogues [9].

This work characterises molecules and methods. It says nothing about what the compound does, and it is cited here because it is the most rigorous published account of what these materials are.

Current Research Status

Regulatory status (United States)
Not approved. CJC-1295 has not been approved by the U.S. Food and Drug Administration for any indication.
Investigational status
Developed by ConjuChem Inc. Early-phase clinical work in healthy adults was published in 2006. A phase 2 trial in HIV-associated visceral obesity was registered with a planned enrolment of 120 participants and is recorded in the trial register as terminated. No approval followed and no active clinical development programme has been identified.
Highest research phase reached
Phase 2 (terminated)
Approved uses
None
Approval is compound-specific
No

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

CJC-1295 is a modified 30-residue peptide. The chain recorded in the FDA/NCATS Global Substance Registration System under UNII 62RC32V9N7 is YaDAIFTQSYRKVLAQLSARKLLQDILSRK, written with a lower-case letter at position 2 to mark D-alanine.

The register's chain is not the whole structure. The GSRS record carries one structural modification on that sequence: a substitution at lysine 30 with the maleimidopropionamide derivative that performs the albumin conjugation. The single-letter string therefore describes the backbone, not the complete covalent molecule.

The substitutions are at four positions. Against the sermorelin sequence — human GHRH 1-29, recorded under UNII 89243S03TE — residues 1 to 29 of this molecule differ at position 2 (D-alanine for L-alanine), position 8 (glutamine for asparagine), position 15 (alanine for glycine) and position 27 (leucine for methionine).

The identifiers agree across registers. CAS registry number 446262-90-4 and PubChem compound identifier 91971820 both resolve to this substance, and the molecular formula C165H269N47O46 and molecular weight 3647.2 g/mol are consistent between them and the supplier catalog. A different registry number circulates in some commercial listings; the number published here is the register's.

Analytical Specifications

Physical form
Lyophilized powder
Appearance
White to off-white lyophilized solid
Lot number
RP-2609-061
Tested purity
≥99% by HPLC
Storage
−20 °C, protect from light, desiccate

Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.

Frequently Asked Questions

What is CJC-1295 DAC?
CJC-1295 DAC is a synthetic analogue of human growth hormone-releasing hormone built on the 1-29 fragment, with four amino acid substitutions and an additional C-terminal lysine carrying a maleimidopropionamide group. That group reacts with the free thiol on cysteine 34 of serum albumin, forming a covalent conjugate that circulates far longer than the free peptide [3]. It is a laboratory reagent and an investigational compound, not an approved medicine.
What does DAC stand for in CJC-1295?
Drug affinity complex — the albumin-binding chemistry described above. The abbreviation exists to distinguish the conjugating molecule from CJC-1295 no DAC, the same substituted 29-residue chain without the conjugating group. Analytical chemists treat the two as separate analytes [9].
How does CJC-1295 DAC work?
It is an agonist at the growth hormone-releasing hormone receptor, a class B1 G protein-coupled receptor on pituitary somatotrophs that signals through Gs and cyclic AMP [2]. The substituted backbone resists dipeptidylpeptidase IV, the enzyme that cleaves the native hormone at the 2-3 bond within minutes [1], and albumin conjugation extends circulation from minutes to days [3].
What plasma half-life has been reported for CJC-1295?
In two randomised placebo-controlled ascending-amount trials in healthy adults, the estimated half-life was 5.8 to 8.1 days [4]. A separate study in healthy men described the analogue as having a half-life of about eight days [6]. Those figures describe the pharmaceutical-grade investigational material administered in those trials.
Is CJC-1295 FDA approved?
No. CJC-1295 has not been approved by the U.S. Food and Drug Administration for any indication. Approval in the United States is specific to a compound and an indication.
Has CJC-1295 DAC been studied in humans?
Yes, in early-phase work. Two randomised, placebo-controlled, double-blind ascending-amount trials of 28 and 49 days were conducted in healthy adults [4]; a separate study assessed overnight growth hormone secretion patterns in healthy men aged 20 to 40 [6]; and serum from eleven healthy young adult men was analysed for proteomic change one week after administration [7].
How far did clinical development of CJC-1295 get?
To phase 2. A multicentre, randomised, placebo-controlled, double-blind phase 2 study of twelve weeks in participants with HIV-associated visceral obesity was registered by ConjuChem with a planned enrolment of 120 and is recorded in the trial register as terminated [10]. No approval followed.
How does CJC-1295 DAC differ from CJC-1295 no DAC?
By one residue and one functional group. CJC-1295 no DAC is the substituted 29-residue chain; CJC-1295 DAC adds a thirtieth residue, a lysine bearing the maleimidopropionamide group that bonds to albumin [3]. The conjugating form is the one with a published human literature; the unconjugated form has none.

Scientific References

  1. Frohman LA, Downs TR, Heimer EP, et al.. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma The Journal of clinical investigation; 1989. PMID 2565342 doi:10.1172/JCI114049
  2. Gaylinn BD, Harrison JK, Zysk JR, et al.. Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone Molecular endocrinology (Baltimore, Md.); 1993. PMID 7680413 doi:10.1210/mend.7.1.7680413
  3. Jetté L, Léger R, Thibaudeau K, et al.. 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. PMID 15817669 doi:10.1210/en.2004-1286
  4. Teichman SL, Neale A, Lawrence B, et al.. 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 The Journal of clinical endocrinology and metabolism; 2006. PMID 16352683 doi:10.1210/jc.2005-1536
  5. Alba M, Fintini D, Sagazio A, et al.. 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. PMID 16822960 doi:10.1152/ajpendo.00201.2006
  6. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog The Journal of clinical endocrinology and metabolism; 2006. PMID 17018654 doi:10.1210/jc.2006-1702
  7. Sackmann-Sala L, Ding J, Frohman LA, et al.. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society; 2009. PMID 19386527 doi:10.1016/j.ghir.2009.03.001
  8. Timms M, Ganio K, Steel R. A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS Drug testing and analysis; 2019. PMID 30938069 doi:10.1002/dta.2599
  9. Memdouh S, Gavrilović I, Ng K, et al.. Advances in the detection of growth hormone releasing hormone synthetic analogs Drug testing and analysis; 2021. PMID 34665524 doi:10.1002/dta.3183
  10. A Study to Evaluate CJC 1295 in HIV Patients With Visceral Obesity 2005. NCT00267527

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

Related laboratory reagent: CJC-1295 DAC specifications and lot documentation