CJC-1295 with DAC: A Research Overview

Introduction

CJC-1295 with DAC is a synthetic peptide analog of growth hormone-releasing hormone (GHRH) incorporating a proprietary Drug Affinity Complex (DAC) modification. The DAC technology extends the compound's circulatory residence time through covalent binding to endogenous serum albumin, making it one of the longest-acting synthetic GHRH analogs documented in peer-reviewed literature. Classified as a GHRH analog and growth-hormone secretagogue, it has been the subject of published pharmacokinetic and pharmacodynamic research since the early 2000s. This article provides an educational reference summary of the compound's chemical identity, pharmacological classification, and regulatory context based on published primary literature and regulatory documents.

Background

Growth hormone-releasing hormone (GHRH) is a hypothalamic neuropeptide that stimulates somatotroph cells in the anterior pituitary to synthesize and release growth hormone (GH). Native GHRH has a biological half-life measured in single-digit minutes owing to rapid N-terminal cleavage by dipeptidyl peptidase-4 (DPP-4) in plasma, which converts the full-length biologically active peptide to a truncated, essentially inactive metabolite [1]. This pharmacokinetic limitation has driven decades of research into stabilized synthetic analogs that retain GHRH receptor agonism while resisting rapid proteolysis.

The first FDA-approved GHRH analog with clinical application was sermorelin, a synthetic 29-amino acid fragment (GHRH 1–29) approved for diagnostic and pediatric therapeutic use. A later GHRH analog, tesamorelin — a 44-amino acid synthetic peptide — received FDA approval in 2010 for a specific approved indication [2]. CJC-1295 with DAC represents a distinct research-stage approach in which the half-life limitation was addressed through an albumin-binding conjugation strategy, contributing a novel structural pharmacology to the GHRH analog class.

Chemistry and Structure

CJC-1295 with DAC is a 30-amino acid synthetic peptide derived from the human GHRH(1-29) sequence. Relative to the native GHRH(1-29) scaffold (sermorelin), CJC-1295 incorporates four amino acid substitutions intended to confer resistance to enzymatic cleavage. These substitutions modify residues at positions 2, 8, 15, and 27 of the native sequence, collectively referred to as the tetra-substituted scaffold [3].

The DAC component — the feature that distinguishes CJC-1295 with DAC from structurally related analogs — is an N-epsilon-3-maleimidopropionamide derivative of lysine appended at the C-terminus of the peptide. This reactive maleimide group selectively and rapidly forms a covalent thioether bond with the Cys34 free thiol on circulating human serum albumin (HSA) following administration. The resulting covalent peptide-albumin conjugate retains biological activity at the GHRH receptor while benefiting from albumin's extended circulatory half-life [3].

Bhatt and colleagues first characterized this conjugation chemistry in the context of GHRH analogs, reporting a 4-fold increase in GH area under the curve for CJC-1295 compared with hGRF(1-29) in rat models, along with markedly enhanced in vitro stability against DPP-4 degradation for the albumin conjugate [3].

The molecular formula of CJC-1295 is C165H269N47O46, with a molecular weight of approximately 3,647 daltons for the unconjugated peptide. The albumin-conjugated form circulates at the effective molecular weight of albumin (~67 kDa) plus the peptide.

Pharmacological Classification

CJC-1295 with DAC is classified as a synthetic GHRH analog and a growth-hormone secretagogue. Its pharmacological action is mediated through agonist binding at the GHRH receptor (GHRH-R), a class B1 secretin-family G protein-coupled receptor expressed predominantly on anterior pituitary somatotroph cells [4].

This pharmacological classification places CJC-1295 with DAC in the same mechanistic family as sermorelin and tesamorelin, but with a distinct structural and pharmacokinetic profile attributable to the DAC modification. Unlike direct GH administration, GHRH analogs act upstream of the pituitary and do not directly supply exogenous GH; they engage the endogenous pituitary signaling pathway.

The compound should not be confused with CJC-1295 without DAC, also known as Modified GRF(1-29) or Mod-GRF(1-29), which carries the same four-amino-acid substitutions but lacks the maleimide-albumin conjugation chemistry and therefore has a substantially shorter half-life.

Discovery History

The discovery of CJC-1295 with DAC arose from the intersection of two research lineages: the pharmacology of synthetic GHRH analogs and the development of albumin-conjugation technology for extending peptide half-lives.

The GHRH molecular sequence was first isolated in 1982 by two independent research groups. Guillemin and colleagues reported isolation of a 44-amino acid growth hormone-releasing factor from a human pancreatic tumor associated with acromegaly, publishing the primary sequence and demonstrating its GH-stimulating activity [6]. Concurrently, Rivier, Spiess, Thorner, and Vale at the Salk Institute characterized a structurally related peptide from the same disease context. These parallel discoveries established the molecular identity of GHRH and launched subsequent analog programs.

The DAC platform was developed by ConjuChem Inc. (Montreal, Canada), a biotechnology company focused on reactive-chemistry approaches to peptide half-life extension. The first peer-reviewed characterization of CJC-1295 as a long-lasting GHRH analog was published in 2005 by Bhatt and colleagues in Endocrinology, reporting the preclinical identification and pharmacological characterization of the compound [3]. Human pharmacokinetic and pharmacodynamic data followed in 2006, reported by Teichman and colleagues in the Journal of Clinical Endocrinology and Metabolism, establishing the compound's extended half-life and GH/IGF-1 axis responses in healthy adult volunteers [7].

Regulatory Status

CJC-1295 with DAC has not received regulatory approval from the US Food and Drug Administration (FDA) or any comparable regulatory authority for any therapeutic indication in humans. It is not listed in the FDA Orange Book as an approved drug product.

In December 2024, the FDA's Pharmacy Compounding Advisory Committee (PCAC) evaluated five CJC-1295-related substances in the context of their potential inclusion on the Section 503A bulk drug substances list governing pharmacy compounding [5]. A ConjuChem-sponsored Phase 2 clinical trial in HIV-associated visceral obesity (ClinicalTrials.gov NCT00267527) generated human-study context for the compound, though the trial was not completed and results were not published in peer-reviewed form. These regulatory milestones are chronicled in detail in the companion CJC-1295 with DAC history article. Research-grade CJC-1295 with DAC from SpartaLabs is verified by independent third-party HPLC and mass spectrometry analysis for each batch.

The World Anti-Doping Agency (WADA) classifies GHRH and its analogs, including CJC-1295, as prohibited substances under Section S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics) of the Prohibited List.

CJC-1295 with DAC is sold and studied as a research-use-only (RUO) compound. Its regulatory status is distinct from that of approved pharmaceuticals.

References

1. Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J Clin Invest. 1989;83(5):1533-1540. PMID: 2703532. PMC: PMC303858.

2. Falutz J, Allas S, Blot K, Potvin D, Kotler D, Somero M, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. N Engl J Med. 2007;357(23):2359-2370. PMID: 19243281. DOI: 10.1056/NEJMoa072688.

3. Bhatt DL, Bhatt S, Gagnon C, Castaigne JP, Frohman LA. 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;146(9):3810-3818. PMID: 15817669. DOI: 10.1210/en.2004-1611.

4. Frohman LA, Kineman RD. Growth hormone-releasing hormone receptor (GHRH-R) and its signaling. Rev Endocr Metab Disord. 2025. PMC: PMC12137518.

5. US Food and Drug Administration. Pharmacy Compounding Advisory Committee (PCAC) Meeting Briefing Document. December 4, 2024. Available at: https://www.fda.gov/media/183819/download.

6. 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. PMID: 6812220. DOI: 10.1126/science.6812220.

7. 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. PMID: 16352683. DOI: 10.1210/jc.2005-1536.