History and Development of CJC-1295 with DAC as a Research Peptide
Research Notice: This article covers the history and scientific development of CJC-1295 with DAC — available from Palmetto Peptides for laboratory use only.
DISCLAIMER: This article is for educational and scientific research reference purposes only. All compounds discussed are not approved by the FDA for use in humans or animals. All data discussed here reflects preclinical animal research or laboratory use. Palmetto Peptides sells these compounds exclusively for in vitro and preclinical laboratory research. Nothing in this article constitutes medical advice.
History and Development of CJC-1295 with DAC as a Research Peptide
Last Updated: May 18, 2026 | Reading Time: Approximately 13 minutes | Author: Palmetto Peptides Research Team
Quick Answer
CJC-1295 with DAC was developed by ConjuChem Biotechnologies, a Montreal-based biopharmaceutical company, during the late 1990s and early 2000s as part of a broader effort to create long-acting analogues of peptide hormones using the company's proprietary Drug Affinity Complex (DAC) technology. The compound emerged from foundational research on growth hormone-releasing hormone (GHRH) analogues and the challenge of their short in vivo half-life. After progressing through preclinical development and Phase I and Phase II clinical trials for growth hormone deficiency, CJC-1295 with DAC's clinical program was ultimately discontinued, but the compound's well-characterized pharmacokinetics and sustained GH-stimulating activity have established it as one of the most widely used tool compounds in preclinical growth hormone axis research.
The Scientific Problem That CJC-1295 with DAC Was Built to Solve
To understand why CJC-1295 with DAC was developed and why its development history matters to researchers using it today, you need to start with the fundamental limitation of native growth hormone-releasing hormone. GHRH is the hypothalamic peptide that drives growth hormone secretion from anterior pituitary somatotrophs. It was identified and characterized in the early 1980s — a landmark achievement that earned Roger Guillemin and Andrew Schally the 1977 Nobel Prize in Physiology or Medicine for related work on hypothalamic regulatory peptides.
Despite its central physiological role, GHRH has essentially no utility as a drug or research tool in its native form. The plasma half-life of human GHRH is somewhere between 2 and 7 minutes under physiological conditions. The enzyme primarily responsible for this rapid degradation is dipeptidyl peptidase-4 (DPP-4), a serine protease that cleaves GHRH at the bond between positions 2 and 3 within minutes of the peptide entering circulation. Even if DPP-4 were inhibited, additional proteases and renal filtration would clear the peptide within tens of minutes.
For researchers who wanted to study what happens when the GHRH axis is activated over hours, days, or weeks, and for clinicians who hoped to treat growth hormone deficiency by stimulating endogenous GH release rather than administering exogenous GH directly, this presented an essentially unsurmountable barrier. The first wave of solutions involved developing DPP-4-resistant GHRH analogues through amino acid substitutions. The second and more transformative wave involved extending half-life through plasma protein binding. CJC-1295 with DAC represents the most successful realization of that second approach.
The Origins of DAC Technology at ConjuChem
ConjuChem Biotechnologies: Background
ConjuChem Biotechnologies was founded in Montreal, Quebec, Canada in the late 1990s with a focus on developing a platform for creating long-acting drug conjugates. The company's core intellectual property centered on what they termed the Drug Affinity Complex technology — a chemical strategy for attaching therapeutic peptides and small molecules covalently to circulating plasma proteins, primarily albumin, to extend their half-lives dramatically.
The scientific rationale behind DAC technology drew on well-established pharmacokinetic principles. Albumin, the most abundant plasma protein, has an extraordinarily long circulatory half-life of approximately 19 days in humans, maintained by the neonatal Fc receptor (FcRn) recycling pathway that rescues albumin from lysosomal degradation and returns it to circulation. If a short-lived therapeutic could be stably attached to albumin, it would inherit this protection, potentially converting a compound with a half-life of minutes into one with a half-life of days.
The challenge was creating a reactive linkage that would form rapidly and selectively in the complex milieu of plasma without requiring pre-conjugation (which would eliminate the benefits of in vivo binding). ConjuChem's solution was to engineer a maleimido-propionic acid NHS ester group onto the compound, targeting the highly reactive free thiol group of cysteine-34 (Cys34) on albumin — essentially the only accessible free thiol in normal plasma at physiological concentrations adequate for efficient conjugation.
Why Albumin's Cys34 Was the Right Target
The selection of albumin Cys34 as the conjugation target was not arbitrary. Human serum albumin has 17 disulfide bonds involving 34 of its 35 cysteine residues, leaving Cys34 as the only cysteine with a free thiol group under physiological conditions (in approximately 25 to 40% of circulating albumin molecules at any given time). This structural feature makes Cys34 a uniquely accessible and specific target in plasma for reactive thiol chemistry. No other major plasma protein presents a comparable free thiol in a similarly accessible location, which gives the DAC chemistry high selectivity for albumin over other plasma proteins.
Development of CJC-1295: From Concept to Compound
The GHRH Analogue Foundation
Before the DAC modification could be applied, ConjuChem's researchers needed to start with a GHRH analogue that was stable enough to survive in circulation during the time required for albumin conjugation. Native GHRH would be degraded by DPP-4 within minutes, long before the albumin-binding reaction could proceed to useful completion.
The team built on two decades of published literature on GHRH analogue design. The critical substitutions established earlier in the field — particularly the replacement of L-alanine at position 2 with D-alanine to block DPP-4 cleavage — were incorporated into the CJC-1295 backbone. Additional modifications were made to address other sites of proteolytic vulnerability and chemical instability, including replacement of methionine at position 27 with norvaline (to prevent oxidation) and asparagine at position 8 with glutamine (to prevent deamidation).
The resulting backbone, based on the biologically active GHRH(1-29) fragment, was DPP-4-resistant and chemically stable enough to survive the hours needed for plasma albumin conjugation, while retaining sufficient GHRH receptor binding affinity to produce GH secretion once the albumin-bound form was circulating.
Attaching the DAC Linker
With a stable GHRH(1-29) backbone in hand, the DAC linker was attached via the epsilon-amino group of a lysine residue appended to the C-terminus of the sequence, designated Lys30. Placement at the C-terminus was deliberate: the biological activity of GHRH resides primarily in the N-terminal region of the peptide, and attaching the albumin-reactive group at the opposite end minimized interference with GHRH receptor engagement. The full compound — GHRH(1-29) analogue with D-Ala2 and other stabilizing substitutions, plus a C-terminal lysine bearing the DAC maleimide-NHS ester linker — was designated CJC-1295.
The name follows ConjuChem's internal compound numbering convention; the specific rationale for the number 1295 is not disclosed in published literature, but it reflects ConjuChem's library designation system for conjugate compounds. The "with DAC" designation distinguishes it from CJC-1295 without DAC (also known as Modified GRF 1-29 or Mod GRF), a compound that uses the same GHRH backbone with the same stabilizing substitutions but lacks the albumin-reactive DAC linker.
The Development Timeline: Key Milestones
| Period | Milestone | Significance |
|---|---|---|
| Late 1990s | ConjuChem develops DAC platform technology | Foundation for in vivo albumin-reactive conjugation chemistry |
| Early 2000s | CJC-1295 synthesized and characterized in vitro | Demonstrates albumin binding, DPP-4 resistance, and preserved GHRHR activity |
| 2003 to 2004 | Preclinical rodent and primate studies completed | Demonstrates 6 to 8 day half-life in animal models; sustained GH and IGF-1 elevations documented |
| 2005 | Landmark Endocrinology paper published (Jetté et al.) | First peer-reviewed characterization of CJC-1295 albumin binding, pharmacokinetics, and GH-stimulating activity in rats |
| 2006 | Phase I/II human clinical trial data published (Teichman et al.) | First published human pharmacokinetic and GH/IGF-1 data; estimated human half-life of approximately 6 to 8 days confirmed |
| Mid-2000s | ConjuChem pursues broader clinical program for GH deficiency | CJC-1295 enters Phase II trials for adult growth hormone deficiency |
| 2008 to 2010 | ConjuChem clinical program discontinued | Compound development as a pharmaceutical agent ceases; CJC-1295 enters research chemical domain |
| 2010 onward | CJC-1295 with DAC widely adopted as preclinical research tool | Becomes one of the most cited long-acting GHRH analogues in GH axis research; synthesized by multiple research chemical suppliers |
The 2005 Endocrinology Paper: Establishing CJC-1295 in the Literature
The paper by Jetté et al., published in Endocrinology in 2005, represents the scientific foundation on which all subsequent research with CJC-1295 with DAC has been built. The authors characterized the compound's albumin-binding chemistry in detail, confirmed its DPP-4 resistance, and documented its pharmacokinetics and pharmacodynamics in rat models.
The key findings from this paper that entered the research community's working knowledge of the compound include:
- The compound forms a stable covalent thioether bond with albumin Cys34 via Michael addition of the maleimide group to the free thiol
- In rats, mean plasma half-life was approximately 5.8 days — dramatically longer than native GHRH or unmodified GHRH analogues
- A single injection produced GH elevations measurable for approximately 7 days and IGF-1 elevations measurable for approximately 9 to 11 days in rodents
- The albumin-bound form retained GHRH receptor binding and biological activity, despite the large albumin molecule tethered to the C-terminus
This paper established CJC-1295 with DAC as a legitimate research tool with a clear mechanism, reproducible pharmacokinetics, and documented biological activity. Its citation in hundreds of subsequent publications speaks to how thoroughly it has been integrated into the GH axis research literature.
The 2006 Clinical Trial Publication: Teichman et al.
The following year, Teichman and colleagues published Phase I/II data from a human study in the Journal of Clinical Endocrinology and Metabolism. This study administered CJC-1295 with DAC to healthy adult volunteers at multiple dose levels and characterized its pharmacokinetics and effects on GH and IGF-1 secretion in humans.
The human data confirmed the long half-life predicted from animal models, with estimates of approximately 6 to 8 days in humans. Single doses produced GH and IGF-1 elevations that persisted for up to two weeks. The compound was generally well-tolerated in this healthy volunteer population at the doses tested. These findings positioned CJC-1295 with DAC as a plausible candidate for weekly or bi-weekly dosing regimens in a potential GH deficiency treatment context.
From the research community's perspective, this clinical publication added an important layer of translational context to the preclinical data: the pharmacokinetic principles established in rats were broadly validated in a human pharmacokinetic setting, lending confidence to the use of the compound as a preclinical tool for modeling sustained GHRH axis activation.
Why ConjuChem's Clinical Program Did Not Continue
Despite the promising preclinical and early clinical data, ConjuChem's development of CJC-1295 with DAC as a pharmaceutical product did not progress to late-stage clinical trials or regulatory approval. The specific reasons for the discontinuation of the clinical program are not fully documented in the public record, which is typical for pharmaceutical development decisions that are made for commercial, strategic, or scientific reasons not always disclosed by companies.
Several factors in the broader context of GH research and drug development at the time are relevant. The GH deficiency treatment market was already well-served by recombinant human GH (rhGH) products administered daily or with long-acting formulations using PEGylation or other technologies. Demonstrating that a GHRH analogue produced equivalent or superior clinical outcomes to direct rhGH replacement — while meeting the regulatory burden of Phase III trials — represented a significant and expensive clinical development challenge. The commercial case for a new mechanism-of-action approach in an established therapeutic category, for a company of ConjuChem's scale, was challenging.
Additionally, the broader financial difficulties that affected many small biopharmaceutical companies during the late 2000s, particularly in the period following the 2008 financial crisis, likely contributed to the contraction of ConjuChem's clinical programs.
Transition to the Research Chemical Domain
The Path from Clinical Candidate to Research Tool
The discontinuation of ConjuChem's clinical program created the conditions for CJC-1295 with DAC to become widely available as a research chemical. The compound's chemistry was described in detail in peer-reviewed publications and patents that entered the public domain. Multiple peptide synthesis laboratories began producing CJC-1295 with DAC for research use, and the compound became available through research chemical suppliers as early as the late 2000s.
From a research utility standpoint, the transition from clinical candidate to tool compound was in many respects favorable. Researchers did not need to navigate clinical development constraints; they simply needed a compound with reproducible pharmacokinetics and documented biological activity for use in preclinical models. CJC-1295 with DAC met these criteria precisely. Its well-characterized albumin-binding mechanism, known half-life, and published pharmacodynamic data made it immediately useful as a tool for studying the GH axis in controlled laboratory settings.
Role of the 2005 and 2006 Publications in Sustaining Research Interest
A key reason CJC-1295 with DAC remained prominent in the research literature after ConjuChem's clinical program ended was the quality and completeness of the 2005 and 2006 publications. Unlike many research chemicals whose preclinical characterization remains fragmentary or only in conference abstracts, CJC-1295 with DAC had a thorough mechanistic description, validated pharmacokinetic data from multiple species, and even early human data available in peer-reviewed journals. Researchers could cite a clear scientific foundation for using the compound, which facilitated its adoption in grant-funded preclinical studies.
CJC-1295 Without DAC: The Related But Distinct Compound
A source of ongoing confusion in the research literature and among researchers sourcing compounds is the distinction between CJC-1295 with DAC and CJC-1295 without DAC (also called Modified GRF 1-29 or Mod GRF 1-29). Understanding this distinction requires appreciating the development history.
| Feature | CJC-1295 with DAC | CJC-1295 without DAC (Mod GRF 1-29) |
|---|---|---|
| DAC linker present | Yes | No |
| In vivo albumin binding | Yes (covalent, irreversible) | No |
| Plasma half-life | 6 to 8 days | 20 to 30 minutes |
| GH response duration | Days to over a week | Minutes to a few hours |
| DPP-4 resistance | Yes | Yes (same backbone substitutions) |
| ConjuChem original compound | Yes | No (DAC removed; variant developed separately) |
Modified GRF 1-29 uses the same DPP-4-resistant GHRH backbone with the same stabilizing amino acid substitutions as CJC-1295 with DAC, but lacks the albumin-reactive maleimide linker on the C-terminal lysine. The result is a compound with a half-life measured in tens of minutes rather than days. Modified GRF 1-29 entered the research chemical market alongside CJC-1295 with DAC but serves a different experimental purpose: providing a shorter-acting GHRH stimulus rather than the multi-day sustained activation that CJC-1295 with DAC provides.
Researchers must be aware of this distinction when sourcing compounds and when reading the literature, as some publications or supplier descriptions conflate or mislabel the two compounds. The key identifier is the presence or absence of the DAC (maleimide) modification, which is reflected in the compound name, its pharmacokinetic profile, and its mass spectrometry data.
CJC-1295 with DAC in the Context of the Broader GHRH Analogue Landscape
Sermorelin: The Earlier Approach
Before CJC-1295 with DAC, the most prominent GHRH analogue in both research and clinical use was sermorelin (GHRH 1-29 amide), which reached approval for GH deficiency in children in the United States in 1997 under the brand name Geref. Sermorelin is the unmodified biologically active fragment of GHRH, differing from native GHRH primarily in being truncated at position 29 rather than using the full 44-amino acid sequence. While sermorelin had sufficient GHRH receptor activity for clinical use, it shared GHRH's fundamental DPP-4 sensitivity and short plasma half-life, requiring daily administration.
CJC-1295 with DAC can be understood in historical context as an attempt to solve the fundamental limitation that sermorelin could not address: duration of action. Where sermorelin needed daily injection, CJC-1295 with DAC was designed for weekly or less frequent administration — a meaningful therapeutic and experimental improvement.
Tesamorelin: The Alternative Approach
Tesamorelin (trade name Egrifta) pursued a different solution to the GHRH stability problem. Rather than using albumin binding, tesamorelin employed a trans-3-hexenoic acid modification at the N-terminus of the full 44-amino acid GHRH sequence to improve stability. Tesamorelin received FDA approval in 2010 for HIV-associated lipodystrophy, becoming the only GHRH analogue to receive full regulatory approval in the United States. Its half-life is measured in hours rather than days, still requiring daily administration, but it represented a successful regulatory path that CJC-1295 with DAC's clinical program did not complete.
Legacy: CJC-1295 with DAC as a Research Standard
Despite — and in some ways because of — its discontinuation as a pharmaceutical development candidate, CJC-1295 with DAC has achieved a durable place in the preclinical research toolkit. The characteristics that made it appealing as a potential drug (long half-life, preserved receptor activity, reproducible pharmacokinetics, well-tolerated in early clinical study) are precisely the characteristics that make it valuable as a research tool.
Researchers studying the consequences of sustained GHRH axis activation — on body composition, bone metabolism, muscle physiology, IGF-1 biology, hepatic function, and GH pulse architecture — have found CJC-1295 with DAC to be a reliable, mechanistically transparent, and scientifically well-grounded tool compound. The fact that its pharmacokinetics have been characterized not only in rodents but also in primates and humans adds an unusual degree of translational confidence for a preclinical research tool.
For a detailed examination of the compound's mechanism of action, see our article on CJC-1295 DAC mechanism of action and Drug Affinity Complex half-life. For pharmacokinetic data, see our article on CJC-1295 DAC pharmacokinetics and half-life in preclinical models.
Researchers sourcing CJC-1295 with DAC today benefit from a compound whose development history spans nearly three decades of scientific scrutiny. To procure research-grade CJC-1295 with DAC for laboratory use, Palmetto Peptides provides verified purity documentation and appropriate research-grade specifications.
Frequently Asked Questions
Who invented CJC-1295 with DAC and when?
CJC-1295 with DAC was developed by ConjuChem Biotechnologies, a Montreal-based biopharmaceutical company, during the late 1990s and early 2000s. The compound's development drew on earlier work on GHRH analogues and on ConjuChem's proprietary Drug Affinity Complex technology for creating long-acting albumin-conjugating peptides. The first peer-reviewed publication describing CJC-1295 appeared in the journal Endocrinology in 2005, authored by Jetté and colleagues at ConjuChem.
What does the name CJC-1295 mean?
CJC is ConjuChem's company abbreviation, used as a prefix for their compound library. The number 1295 is ConjuChem's internal compound designation and does not carry a specific chemical or structural meaning in the published literature. The "with DAC" qualifier distinguishes the albumin-binding version from Modified GRF 1-29 (CJC-1295 without DAC), which shares the same GHRH backbone but lacks the albumin-reactive maleimide linker.
Why did ConjuChem stop developing CJC-1295 as a pharmaceutical?
The full reasons for the discontinuation of ConjuChem's CJC-1295 clinical program are not documented in the public record. The most likely factors include the challenges of demonstrating clinical differentiation from existing rhGH replacement therapies in a Phase III trial setting, the financial pressures on small biopharmaceutical companies during the late 2000s, and the significant cost of late-stage clinical development in an already-competitive GH deficiency market.
What is the difference between CJC-1295 with DAC and CJC-1295 without DAC?
The only structural difference is the presence or absence of the Drug Affinity Complex linker — a maleimido-propionic acid NHS ester group — on the C-terminal lysine. With the DAC linker present, the compound binds covalently to albumin Cys34 in vivo, producing a half-life of 6 to 8 days. Without the DAC linker (Modified GRF 1-29), the compound lacks albumin binding and has a plasma half-life of approximately 20 to 30 minutes. Both share the same DPP-4-resistant GHRH backbone.
When did CJC-1295 with DAC become available as a research chemical?
CJC-1295 with DAC began appearing in the research chemical market in the late 2000s following the disclosure of its structure in peer-reviewed publications and patents. By the early 2010s it was available from multiple research-grade peptide suppliers and had been adopted widely in preclinical GH axis research. Its availability accelerated after ConjuChem's clinical program wound down and the compound transitioned fully into the research tool domain.
How does the history of CJC-1295 compare to other GHRH analogues like sermorelin and tesamorelin?
Sermorelin (approved 1997) was the earlier approach — an unmodified GHRH fragment with a short half-life requiring daily dosing. Tesamorelin (approved 2010) used a fatty acid modification to improve stability but still requires daily dosing and is approved only for HIV-associated lipodystrophy. CJC-1295 with DAC pursued the most aggressive half-life extension strategy of any GHRH analogue using covalent albumin binding, reaching early clinical trials but not regulatory approval. It remains the longest-acting GHRH analogue commonly used in preclinical research.
Why is the 2005 Jetté et al. paper so important to understanding CJC-1295 with DAC?
The 2005 Endocrinology paper by Jetté and colleagues was the first peer-reviewed publication to characterize CJC-1295 with DAC in detail — describing the albumin-binding chemistry, confirming DPP-4 resistance, documenting pharmacokinetics in rats, and demonstrating sustained GH and IGF-1 elevations after a single injection. It provided the scientific foundation that all subsequent researchers could build on, and its thoroughness meant the compound entered the literature with unusually strong mechanistic documentation for a research tool compound.
Peer-Reviewed Citations
- 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-lived GRF analog. Endocrinology. 2005;146(7):3052-3058. doi:10.1210/en.2004-1624
- 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 and Metabolism. 2006;91(3):799-805. doi:10.1210/jc.2005-1536
- 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. doi:10.1126/science.6812220
- Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. Journal of Clinical Investigation. 1989;83(5):1533-1540. doi:10.1172/JCI114048
- Kontermann RE. Strategies for extended serum half-life of protein therapeutics. Current Opinion in Biotechnology. 2011;22(6):868-876. doi:10.1016/j.copbio.2011.06.012
- Falutz J, Allas S, Blot K, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359-2370. doi:10.1056/NEJMoa072375
- Alba M, Fintini D, Bhatt H, et al. Effects of long-term treatment with CJC-1295, a long-acting growth hormone-releasing hormone analog, in GH-deficient rats. American Journal of Physiology Endocrinology and Metabolism. 2006;291(6):E1208-E1215. doi:10.1152/ajpendo.00201.2006
- Müller EE, Locatelli V, Cocchi D. Neuroendocrine control of growth hormone secretion. Physiological Reviews. 1999;79(2):511-607. doi:10.1152/physrev.1999.79.2.511
Final Disclaimer: All compounds discussed are research chemicals not approved by the FDA for human or veterinary use. All content here is for scientific and educational reference only. Palmetto Peptides sells these products exclusively for in vitro and preclinical laboratory research.
Authored by the Palmetto Peptides Research Team | Last Updated: May 18, 2026