Molecule guides
CJC-1295 No DAC (Modified GRF 1-29): Substitutions, Receptor Action and Research Use
The short-acting GHRH analogue: four engineered residues, one receptor, and why a brief exposure window is often exactly what a study needs.
Modified GRF 1-29 is the correct designation for what most suppliers list as CJC-1295 without DAC. It is a 29-amino-acid synthetic analogue that keeps the part of growth hormone-releasing hormone the receptor recognises, but carries engineered residues in four places (2, 8, 15 and 27) that shut off the three chemical decay pathways of the natural fragment. The common name is a market convention: papers describing CJC-1295 were describing the albumin-tethered drug-affinity-complex molecule, while material labelled no DAC lacks that conjugation entirely and acts on a completely different timescale.
What follows covers the job done by each engineered residue, the receptor pharmacology, the experimental value of rapid clearance, and the checks that confirm you have the right material.
Structure: four substitutions for three problems
Sermorelin, which is the unaltered GHRH (1–29) amide, has three documented chemical vulnerabilities. Each one is neutralised at a particular site in the analogue.
Alanine becomes D-alanine at site 2. The enzyme DPP-4 severs the chain just past that point, stripping away the pair of residues that insert into the receptor's transmembrane pocket, so cleavage equals inactivation. Flipping the chirality of that alanine keeps the side chain identical yet denies the protease the geometry it needs. The bulk of the compound's added durability traces back to this substitution alone.
Asparagine becomes glutamine at site 8. Left in place, and particularly with a small neighbour downstream, asparagine loses its amide group by itself, cyclising into a succinimide that resolves into aspartate and isoaspartate species while the vial sits in storage. Glutamine's longer side chain makes that ring difficult to form, which eliminates the route.
Glycine becomes alanine at site 15. Because glycine lets the chain flex far more than other residues, replacing it tightens local geometry, and published structure-activity data associate the swap with greater potency.
Methionine becomes leucine at site 27. Air exposure turns methionine into its sulfoxide, the source of the +16 Da companion peak seen on sermorelin certificates. Leucine occupies almost the same space but has no sulfur to oxidise, which explains why this analogue's empirical formula lists no sulfur while sermorelin's does.
Collectively the four edits harden a fragile laboratory peptide without touching the C-terminal amide or the parent molecule's affinity for its target.
Mechanism
The compound is an agonist at the GHRH receptor. Occupancy of that receptor on somatotroph cells of the pituitary couples through Gs, elevates cyclic AMP and engages protein kinase A, which both transcribes the growth hormone gene and empties stored granules. Because inhibition by somatostatin and negative feedback from IGF-1 are untouched, secretion remains under normal physiological control.
Against CJC-1295 with DAC, the difference lies purely in how long the molecule persists. Absent a maleimide arm binding it permanently to albumin, elimination is quick, with a reported half-life on the order of thirty minutes instead of several days. Researchers generally treat this as useful rather than deficient. Short persistence delivers one clean episode of receptor stimulation, which is precisely what is needed to examine episodic GHRH signalling, the recovery of the receptor between events, and the endogenous cadence of the somatotropic axis. Uninterrupted occupancy, the property of the DAC form, addresses other questions and invites desensitisation.
Research to date
Structure-activity studies
When laboratories characterise agonists at this receptor, the analogue is a standard benchmark set beside the native fragment, sermorelin and the longer stabilised molecules. It earns that role by being durable enough for reproducible numbers while still clearing quickly, so persistence never confounds the comparison.
Pulsatile signalling and receptor pharmacology
Work in cells and animals measuring second-messenger accumulation, pituitary cell responsiveness and hormone release profiles selects this molecule specifically because each stimulus can be resolved on its own. Our article CJC-1295 vs CJC-1295 with DAC handles the long-acting contrast; CJC-1295 vs sermorelin covers the native-fragment contrast.
Combination designs
Most often the analogue is studied together with a ligand for the ghrelin receptor, ipamorelin being the usual partner. The two targets share a cell yet run through separate signalling arms, one via cyclic AMP and the other via phospholipase C, and certain models describe a synergistic rather than merely additive outcome. A ready-mixed vial of CJC-1295 with ipamorelin exists for exactly this design.
Every strand of this literature is laboratory or animal work. The analogue is authorised nowhere and has never been assessed in a controlled clinical trial.
Formats and sizes
We ship CJC-1295 (No DAC) as sealed vials of lyophilized powder: 2 mg (€45), 5 mg (€80) and 10 mg (€130). Given a mass of 3367.93 g/mol, 5 mg works out at roughly 1.48 micromoles, essentially matching the molar content of an equivalent sermorelin vial and making molar-for-molar comparison trivial. Look under GHRH analogs for the family; the albumin-tethered form has its own listing as CJC-1295 with DAC.
Reconstitution and storage in the lab
Take 5 mg and add 2 mL of bacteriostatic water: the result is 2.5 mg/mL, i.e. 2,500 mcg/mL, so a 0.1 mL volume — the 10-unit graduation on a U-100 syringe — delivers 250 mcg. Expressed molar, the stock sits near 742 micromolar, meaning a 10 nanomolar working concentration is about 74,000-fold away and should be reached through serial steps.
Storage is more forgiving here than with comparable peptides, and the reason is molecular rather than procedural: two of the three standard decay routes were engineered away when the methionine and the labile asparagine disappeared. That is not invulnerability. Sealed powder still belongs at −20 °C away from light and moisture, solutions are still split into aliquots and refrigerated, but a certificate run on aged stock will show fewer side products. The peptide storage guide gives the general rules.
Purity and reading the COA
Lots are taken to 99% or better by reversed-phase HPLC, verified by mass and released with a certificate bearing the same lot number. Three points deserve particular attention with this sequence. The expected mass is 3367.93 g/mol, against 3357.93 g/mol for the untouched GHRH (1–29) amide; those 10 daltons are what distinguish the analogue from sermorelin, and since vendors sometimes blur the two, no other single check is as informative. Next, scan the empirical formula for sulfur, whose presence would betray a retained methionine and therefore the native sequence. Finally, bear in mind that mass spectrometry is blind to the difference between D- and L-alanine at site 2, so that detail rests on manufacturing records and supplier documentation unless a dedicated chiral assay was run. Our COA reading guide sets out the reach of each analytical section.
Regulatory position
No authorisation as a medicinal product exists for this analogue, or for anything sold under the CJC-1295 label, in the EU, the United States or any other market, and neither qualifies as a food supplement ingredient. Supply is for laboratory research exclusively.
Related compounds and further reading
Four molecules answer the same durability question at a single receptor: the plain parent fragment sermorelin, the acylated full-length tesamorelin, this substituted analogue, and the albumin-bound DAC form. Ipamorelin, GHRP-2 and GHRP-6 belong to the other arm, acting through the ghrelin receptor; the GH secretagogue landscape explained maps them all.
Questions
Does CJC-1295 without DAC mean Modified GRF 1-29?
It does, and the second name is the precise one. Published descriptions of CJC-1295 concerned the version conjugated to albumin through a drug affinity complex. A vial marked no DAC holds the four-times-substituted GRF 1-29 chain with that linker absent, which changes how long it persists beyond recognition.
What is each substitution for?
Site 2 carries D-alanine so that DPP-4 no longer finds the chirality it requires and cannot cut. Site 8 carries glutamine, removing an asparagine that would otherwise lose its amide through a succinimide ring. Site 15 carries alanine in place of a highly flexible glycine, a change linked to improved potency. Site 27 carries leucine, deleting the one residue that oxidises readily.
How does it differ from sermorelin?
Sermorelin reproduces the natural GHRH (1-29) amide, weighs 3357.93 g/mol, disappears within minutes and is open to both oxidation and deamidation. The analogue shares that chain but with four engineered residues, weighs 3367.93 g/mol and survives far better. Those 10 daltons are the simplest certificate-level way to tell which one you hold.
Why pick the version without DAC?
Many designs call for exposure that stops quickly. With no albumin linkage the molecule is eliminated fast, its half-life quoted near thirty minutes rather than several days, producing one clean stimulus. That suits studies of episodic signalling and of how the receptor recovers between events, whereas unbroken occupancy risks desensitising it.
Can a COA confirm the D-alanine at position 2?
It cannot. The two enantiomers weigh exactly the same, putting them beyond the reach of mass spectrometry, and ordinary reversed-phase chromatography will not dependably separate them either. Confidence comes from manufacturing records and vendor documentation, or from a chiral assay commissioned separately, which standard certificates seldom include.
Why is there no sulfur in the molecular formula?
Site 27 holds leucine where the natural sequence holds methionine, and methionine was the sole sulfur-containing residue present. Deleting it yields the sulfur-free formula C152H252N44O42. Sulfur appearing on paperwork for this product would indicate the native chain had been supplied instead.
How is it reconstituted for laboratory work?
It is simply a calculation. Two millilitres of bacteriostatic water into a 5 mg vial yields 2.5 mg/mL, equal to 2,500 mcg/mL, so the 10-unit graduation on a U-100 syringe, 0.1 mL, carries 250 mcg. Molar terms put the stock around 742 micromolar, leaving roughly 74,000-fold of dilution, taken in stages, to reach 10 nanomolar.
Is CJC-1295 approved anywhere?
It is not. No country has authorised this analogue, or anything marketed under the CJC-1295 name, as a medicinal product, and neither may be used as a food supplement ingredient.