CJC-1295 without DAC is a 29-residue analog of growth hormone-releasing hormone (GHRH), the hypothalamic peptide that signals pituitary somatotrophs to release growth hormone. It is the GHRH(1-29) amide sequence with four amino acid substitutions chosen to slow enzymatic and chemical breakdown, and it is often called Modified GRF(1-29) or tetrasubstituted GRF(1-29).
Researchers use it as a stabilized but still short-acting GHRH receptor agonist. This article explains how it relates to native GHRH and to CJC-1295 with DAC, what each substitution does, how the GHRH receptor signals, and what the literature does and does not cover.
At a glance
- Class: Synthetic GHRH(1-29) analog peptide; GHRH receptor agonist
- Origin: Tetrasubstituted GRF(1-29) backbone described in the ConjuChem work that produced CJC-1295 (Jetté et al., 2005)
- Structure: 29 residues, C-terminal amide; Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2; C152H252N44O42; 3367.9 g/mol; CAS 863288-34-0
- Main research areas: GHRH receptor pharmacology, somatotroph regulation, comparison with albumin-binding analogs, anti-doping detection
- Regulatory status: Not FDA approved for any use; WADA S2
Structure and origin
GHRH was isolated in 1982 from pancreatic tumors that had caused acromegaly, work recounted by Thorner (Thorner, 2008). The native human hormone is 44 amino acids long, but the first 29 residues with a C-terminal amide retain full receptor activity, and GHRH(1-29)NH2 became the template for most synthetic analogs. Its weakness as a research tool is a very short half-life, driven by rapid enzymatic cleavage and chemical instability at specific positions.
The four substitutions in Modified GRF(1-29) address those weak points:
- D-Ala at position 2: replaces L-Ala and blocks cleavage by dipeptidyl peptidase-4, which otherwise removes the first two residues and inactivates the peptide.
- Gln at position 8: replaces Asn, which is prone to deamidation and rearrangement.
- Ala at position 15: replaces Gly, a change associated with stronger helix formation and receptor activity in GHRH analog studies.
- Leu at position 27: replaces Met, removing an oxidation-prone sulfur.
In 2005, Jetté and colleagues at ConjuChem attached maleimide-containing linkers to GRF(1-29) analogs so they would bond covalently to circulating albumin, a strategy the company called Drug Affinity Complex (DAC). Testing these conjugates in rats, they selected CJC-1295, the tetrasubstituted backbone plus a lysine-maleimide extension, as a long-lasting analog (Jetté et al., 2005). CJC-1295 with DAC was later evaluated in healthy adults in a clinical pharmacokinetic study (Teichman et al., 2006).
The version without DAC is the same tetrasubstituted 29-residue backbone with no linker. It does not bind albumin, so it behaves as a free peptide that is cleared far faster than the conjugate. The name “CJC-1295” strictly refers to the DAC molecule, which is why the label “No DAC” or “Modified GRF(1-29)” matters when reading papers or COAs.
Mechanism: what the research shows
The GHRH receptor was cloned from pituitary tissue in 1992 and identified as a G protein-coupled receptor expressed selectively in the anterior pituitary (Mayo, 1992). It belongs to the class B (secretin-family) GPCRs. Ligand binding activates Gs, adenylate cyclase and cAMP production, which drives growth hormone secretion as well as somatotroph proliferation and growth hormone gene transcription (Mayo et al., 2000).
Because CJC-1295 (No DAC) keeps the receptor-binding residues of GHRH(1-29), it is used as a direct receptor agonist in this system. Its signaling is still shaped by the physiological controls on somatotrophs, including inhibitory somatostatin input, which is part of what makes GHRH analogs useful for studying pulsatile regulation rather than simply raising a hormone level.
Key areas of study
GHRH receptor pharmacology
Receptor activation and cAMP assays in pituitary cells and receptor-expressing cell lines are the most direct use. The original cloning work established the cellular tools that later analog studies rely on (Mayo, 1992).
Somatotroph biology
Research on how GHRH regulates somatotroph number and function, including findings from mice with a mutated GHRH receptor, is reviewed by Mayo and colleagues (Mayo et al., 2000). Stabilized agonists give researchers a way to probe these pathways with a more predictable ligand than native GHRH(1-29).
Comparison with albumin-binding analogs
The DAC and non-DAC forms differ mainly in how long they persist, not in the receptor they target. That makes the pair useful for separating effects of receptor activation from effects of exposure time (Jetté et al., 2005).
Analytical detection
Synthetic GHRH analogs are prohibited in sport, so anti-doping laboratories have developed mass spectrometry methods to detect them and their metabolites; a 2021 review summarizes these approaches, including for CJC-1295 and related analogs (Memdouh et al., 2021).
What the evidence does not show
- Much of the published pharmacology concerns native GHRH, sermorelin or CJC-1295 with DAC. Peer-reviewed studies dedicated specifically to the non-DAC tetrasubstituted peptide are comparatively few.
- Clinical evaluation in the CJC-1295 program concerned the DAC conjugate, not this molecule.
- Stability gains from each substitution come from analog studies of GHRH(1-29) generally; direct head-to-head data for this exact sequence are limited.
- CJC-1295 (No DAC) is not an approved drug, and no regulator has evaluated it for any use.
Regulatory status
CJC-1295 (No DAC) is not approved by the FDA for any use. It is covered by the World Anti-Doping Agency’s Prohibited List under S2 (peptide hormones, growth factors, related substances and mimetics). Rogue Compounds sells it as a research reagent only.
Handling and storage in the lab
Keep the lyophilized peptide sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
CJC-1295 (No DAC) is made in small batches for Rogue Compounds. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same COA is posted on the product page and in the COA Library.
View CJC-1295 (No DAC) on Rogue Compounds
References
- Thorner MO. The discovery of growth hormone-releasing hormone: an update. J Neuroendocrinol. 2008;20(6):653-654. PMID 18601685
- Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PMID 1333056
- Mayo KE, et al. Regulation of the pituitary somatotroph cell by GHRH and its receptor. Recent Prog Horm Res. 2000;55:237-266. PMID 11036940
- Jetté L, 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;146(7):3052-3058. PMID 15817669
- Teichman SL, 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. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683
- Memdouh S, et al. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Test Anal. 2021;13(11-12):1871-1887. PMID 34665524
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.