Quick answer
CJC-1295 without DAC (modified GRF(1-29)) is a 29-residue GHRH analog with four protease-resistance substitutions and no albumin-binding linker, so its GHRH-receptor signal is brief and pulse-like, about 3,368 Da in mass.
- Substitutions: D-Ala2, Gln8, Ala15, Leu27
- Mechanism: GHRH receptor, Gs, cAMP, GH synthesis and release
- Handling: lyophilized, cold and dry; concentration = mg ÷ mL, see the calculator
- Product: CJC-1295 (No DAC)
- Status: For laboratory research use only; not for human consumption.
CJC-1295 without DAC, catalogued in the literature as modified GRF(1-29) or mod-GRF(1-29), is a synthetic analog of the active N-terminal portion of human growth-hormone-releasing hormone (GHRH). It carries four protective residue substitutions but no albumin-binding linker, so its signal is brief and pulse-like. This guide covers its identity, history, chemistry, mechanism, preclinical use and bench handling. For laboratory research use only; not for human consumption. The reagent is available as CJC-1295 (No DAC).
What CJC-1295 (No DAC) is
The molecule is built on GHRH(1-29)-amide, the truncated fragment that carries the receptor-activating information of the 44-residue hormone. Four substitutions relative to the native sequence make it a sturdier reagent than the unmodified fragment: D-alanine at position 2, glutamine at position 8, alanine at position 15 and leucine at position 27. The average mass is approximately 3,368 Da (3,367.9 g/mol). Because there is no drug affinity complex, the peptide behaves as a straightforward 29-mer in solution and is cleared from circulation in animal models over minutes to tens of minutes.
That brevity is the point of the reagent. Endogenous GHRH signaling is pulsatile, so a short-acting stabilized analog allows laboratories to ask about onset, decay, recovery between stimuli and receptor resensitization. It occupies an intermediate niche: more stable than sermorelin, shorter-lived than the albumin-binding DAC form. See also the research overview.
| Property | Value or description |
|---|---|
| Common names | CJC-1295 without DAC; modified GRF(1-29); mod-GRF(1-29) |
| Length | 29 amino acids, C-terminal amide |
| Average mass | about 3,367.9 g/mol |
| Substitutions vs native GHRH(1-29) | D-Ala2, Gln8, Ala15, Leu27 |
| Target | Pituitary GHRH receptor (class B GPCR) |
| Persistence in animal models | Minutes to tens of minutes |
| Supplied form | Lyophilized powder |
Discovery and history
GHRH was purified in 1982 from human pancreatic tumors associated with acromegaly by the groups of Guillemin and of Vale and Rivier. Within a short time it was found that the first 29 residues reproduce the full activity of the 44-residue hormone, and that fragment, GHRH(1-29)-amide, became sermorelin. Its weakness as a reagent was lability: dipeptidyl peptidase IV cleaves the Tyr1-Ala2 bond, producing a biologically inactive product (Frohman et al., 1986), and the methionine at position 27 is prone to oxidation.
The response was targeted substitution. Replacing alanine 2 with the D-isomer defeats the peptidase, and swapping methionine 27 for leucine removes the oxidation site, while changes at positions 8 and 15 further reduce degradation. The result, mod-GRF(1-29), kept receptor engagement but survived longer in assay media. The maturing of solid-phase peptide synthesis made short, precisely modified sequences like this reproducible at consistent quality, which is why the analog became a catalog staple rather than a one-off preparation.
The "CJC" prefix comes from ConjuChem, the Canadian company that went on to attach a maleimide linker to the same backbone, creating the albumin-binding DAC molecule described by Jetté and colleagues in 2005. The "no DAC" label was adopted to distinguish the original-style backbone from that long-acting version, and the contrast between the two became a recurring organizing device in GH-axis studies, letting investigators isolate the variable of duration. The no-DAC form is also commonly discussed beside tesamorelin, another stabilized GHRH analog with a different design. Further detail: discovery and history.
Chemical structure and synthesis
Sequence
The modified sequence is 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. Compared with native GHRH(1-29), the N-terminal substitution addresses proteolysis, the position-27 change addresses oxidation, and the glutamine at position 8 and alanine at position 15 reduce additional liabilities in the chain. Conventions for reading such strings are summarized in understanding amino acid sequences.
Absence of the DAC linker
The DAC variant carries an extra C-terminal lysine bearing a maleimidopropionyl group that couples to albumin cysteine-34. The no-DAC peptide has neither, so it cannot form that covalent bond. The structural fork is a single appendage, yet it changes persistence by orders of magnitude, as set out in the DAC versus no-DAC comparison.
Synthesis and purification
Production is by stepwise solid-phase peptide synthesis: protected amino acids are coupled onto a resin-bound chain, the product is cleaved and deprotected, and crude peptide is purified by preparative reverse-phase HPLC to remove truncated and deletion sequences. Lyophilization produces a stable powder (what is lyophilization). Identity and purity are confirmed by analytical HPLC and mass spectrometry. The full account is in the structure and synthesis article.
Mechanism of action
GHRH-receptor engagement
The peptide is proposed to bind the pituitary GHRH receptor, a class B G-protein-coupled receptor on somatotroph cells. Activation of Gs stimulates adenylate cyclase, raises cAMP and activates protein kinase A, which promotes GH gene transcription and the release of stored growth hormone. This is the same cascade used by native GHRH; the substitutions determine how long the ligand survives, not which receptor it engages.
Why the stabilizing swaps matter mechanistically
By resisting dipeptidyl peptidase and related cleavage, the analog maintains a coherent signal in solution longer than unmodified GHRH(1-29). This is the practical basis of its use: a more reproducible ligand concentration over the course of an assay. The no-DAC form still does not bind albumin covalently, so the signal remains short compared with the DAC molecule, as detailed in the mechanism of action article.
Complementary secretagogue pathway
The ghrelin receptor (GHS-R1a) signals mainly through Gq/11, phospholipase C and calcium mobilization, a separate route to the same GH output. Raun and colleagues showed that ipamorelin stimulates GH release through this class of receptor, and GHRH-receptor and secretagogue-receptor inputs are generally described as interacting synergistically in pituitary systems. This is the rationale for pairing designs, discussed in CJC-1295 vs ipamorelin and in the overview of research blends.
Interpreting concentrations
In-vitro concentrations are set by assay design and receptor pharmacology, not by any extrapolation from living systems. Time-course sampling is more informative than single endpoints for a short-acting ligand.
Preclinical research findings
Most work with this analog uses it as a reference reagent rather than as the subject of a stand-alone published program, so the table describes model systems and the questions they answer rather than headline numbers. Where a published finding exists it is cited.
| Model system | Typical readout | What the analog contributes |
|---|---|---|
| Primary rodent pituitary cultures | GH release into medium | Brief, defined GHRH-receptor stimulus with improved stability over sermorelin |
| GHRH-receptor-expressing cell lines | cAMP accumulation, receptor binding | Quantifies potency and onset/decay kinetics |
| Paired designs with a secretagogue such as ipamorelin | GH release, cAMP plus calcium signaling | Tests interaction of GHRH and ghrelin-receptor inputs |
| Comparative studies with the DAC analog | Time-course of GH and IGF-I | Isolates duration as the variable; Jetté et al. 2005 and Teichman et al. 2006 describe the long-acting counterpart |
| Comparisons with tesamorelin and sermorelin | Potency and stability in assay media | Maps the stability-duration spectrum across the GHRH family |
Why a short profile is experimentally useful
A transient signaling window is a feature, not a flaw. Because endogenous GHRH action is pulsatile, a short-acting analog can distinguish onset, signal decay, recovery between stimuli and receptor resensitization. Those questions differ from designs built on prolonged occupancy, which is why the DAC form is chosen for them instead (see the DAC pillar guide). Pituitary-axis timing is also constrained by somatostatin tone, so interpretable designs include matched vehicle controls, concentration series rather than single points, and replicate preparations from more than one vial of a documented lot.
Findings reflect model-system behavior and assay design only. The full set of notes is in the preclinical research article.
Handling, reconstitution and storage
Without the DAC linker the peptide contains no reactive maleimide, so handling is conventional. The substitutions remove the methionine oxidation site, which makes it more robust than native GHRH, but at low concentrations it can still lose material to surface adsorption, so low-bind labware is advisable. Let the vial reach room temperature, add bacteriostatic water slowly down the inner wall, swirl, and never vortex. The generic procedure is in the lyophilized-peptide reconstitution guide; specifics are in CJC-1295 (No DAC) reconstitution and storage; and this worked example for another peptide shows the full bench sequence. The calculator gives any volume.
The rule is concentration (mg/mL) = mass (mg) ÷ diluent (mL). With a molecular weight of 3,367.9 g/mol:
| Vial contents | Diluent added | Concentration | Approx. molarity |
|---|---|---|---|
| 2 mg | 1 mL | 2 mg/mL | about 594 µM |
| 2 mg | 2 mL | 1 mg/mL | about 297 µM |
| 5 mg | 2 mL | 2.5 mg/mL | about 742 µM |
| 10 mg | 2 mL | 5 mg/mL | about 1,485 µM |
Correct for net peptide content on the COA for exact molar work. Keep lyophilized powder cold, dry and away from light; after reconstitution, single-use aliquots frozen at low temperature preserve integrity far better than repeated refrigeration of a stock vial. The common 28-day figure for refrigerated bacteriostatic solutions is a container convention, not a measured stability limit for this peptide. See storing research peptides and bacteriostatic water explained.
Purity, COA and quality
Reproducible results begin with a documented reagent. A useful certificate of analysis reports HPLC purity with the chromatogram itself, an observed mass close to the theoretical 3,368 Da, and a batch number that matches the vial. Typical impurities are deletion and truncated sequences from stepwise synthesis, and oxidized or deamidated variants. A short routine protects weeks of bench work: check the batch against the COA, look at the trace rather than the summary percentage, confirm the mass, and log batch, storage history and preparation date with the experimental record. The COA page shows batch documents, CJC-1295 (No DAC) purity testing explains the checks, and how to read a COA and understanding HPLC purity give the background. Sourcing considerations are collected in where to buy CJC-1295 (No DAC).
Related compounds and comparisons
Choosing a GHRH-receptor agonist for a study usually means weighing options that share a receptor but differ in persistence and design intent.
| Reagent | Design | Use as comparator |
|---|---|---|
| Sermorelin | Unmodified GHRH(1-29)-amide | Shortest-lived baseline |
| CJC-1295 (No DAC) | Four stabilizing substitutions | Short pulse with better assay stability |
| CJC-1295 with DAC | Substitutions plus albumin-binding linker | Sustained exposure |
| Tesamorelin | Modified full-length GHRH | Different stabilization strategy |
| Ipamorelin | Ghrelin-receptor pentapeptide | Separate pathway to the same output |
For paired designs a pre-combined option is the CJC-1295 (No DAC) + Ipamorelin blend; see the CJC-1295 and ipamorelin research overview. Individual vials are listed on the CJC-1295 (No DAC) product page.
Frequently asked questions
What does no DAC mean?
It means the peptide lacks the drug affinity complex, the maleimide-bearing group that couples the DAC variant to albumin. Without it the peptide is the stabilized backbone alone and is cleared far faster in animal models.
Is no-DAC CJC-1295 the same as mod-GRF(1-29)?
The names are used for functionally the same modified GHRH(1-29) backbone. The four substitutions are D-Ala2, Gln8, Ala15 and Leu27.
What does each substitution do?
D-alanine at position 2 blocks dipeptidyl peptidase-4 cleavage, leucine at position 27 replaces an oxidation-prone methionine, and the glutamine at 8 and alanine at 15 reduce other degradation liabilities.
What is the molecular mass?
The theoretical average mass is approximately 3,368 Da (3,367.9 g/mol). A certificate of analysis should list the observed mass beside that figure.
Why pair it with ipamorelin in research?
The GHRH receptor signals through cAMP and the ghrelin receptor through calcium mobilization. Studying both on the same pituitary cells tests how the pathways interact.
Does the no-DAC form bind albumin?
Not through a dedicated coupling group. It lacks the maleimide-bearing lysine of the DAC form, which is why its persistence is much shorter.
Which cell systems are used?
Primary rodent pituitary cultures and cell lines expressing the GHRH receptor, with cAMP accumulation or GH release into the medium as typical readouts.
How is it supplied and stored?
As a lyophilized powder kept cold, dry and dark. After reconstitution, single-use aliquots limit freeze-thaw cycling; see reconstitution and storage.
How do I plan a stock concentration?
Divide peptide mass by diluent volume to get mg/mL, then convert to molarity using 3,367.9 g/mol. The calculator automates this.
What should a certificate of analysis show?
HPLC purity with the trace, observed mass near 3,368 Da, and a batch number matching the vial. Details are in purity testing.
Research Use Only. For laboratory research use only; not for human consumption. Not for veterinary, clinical, or diagnostic purposes. This guide is research education, not usage guidance.
References
- 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.
- Rivier J, Spiess J, Thorner M, Vale W. Characterization of a growth hormone-releasing factor from a human pancreatic islet tumour. Nature. 1982;300(5889):276-278.
- Frohman LA, Downs TR, Williams TC, Heimer EP, Pan YC, Felix AM. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the Tyr1-Ala2 bond. J Clin Invest. 1986;78(4):906-913.
- 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;146(7):3052-3058.
- 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.
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797.
- Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561.