CJC-1295 (no DAC)

What CJC-1295 (no DAC) is

The material sold as "CJC-1295 without DAC" is a synthetic 29-residue peptide amide whose correct name is Modified GRF (1-29), or more precisely tetrasubstituted GRF(1-29)-NH2. Its 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. It is the N-terminal 29 residues of human growth hormone-releasing hormone (GHRH, also called GRF) with four positions changed: D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27. The "DAC" in the commercial name stands for Drug Affinity Complex, and the phrase "no DAC" means this material does not carry one. The naming is the single most confusing thing about the compound and needs explaining.

"CJC-1295" proper is a specific molecule developed by ConjuChem Inc. of Montreal in the early 2000s. It consists of exactly the tetrasubstituted GRF(1-29) sequence above, extended at the C-terminus by a lysine whose side chain carries a maleimidopropionic acid group. After injection the maleimide reacts with the free thiol of cysteine-34 on circulating albumin, covalently attaching the peptide to the most abundant protein in plasma and giving it a half-life of days rather than minutes [10, 11]. The lysine-maleimide unit is the Drug Affinity Complex. Everything in the human and animal literature that uses the name CJC-1295 refers to that albumin-binding conjugate.

What is sold under the name "CJC-1295 no DAC" is the peptide without the terminal lysine-maleimide: the unconjugated tetrasubstituted GRF(1-29) analogue. That peptide was designed in the late 1980s and early 1990s by Felix, Campbell, Bongers and colleagues at Hoffmann-La Roche as part of a programme to make GRF analogues more stable [7, 8], long before ConjuChem used it as the starting point for its conjugate [10]. It has no DAC, does not bind albumin, and has a short half-life in circulation. The name is a market convention rather than a chemical name. This monograph uses "Mod GRF (1-29)" for the material we supply and "CJC-1295" for the conjugate.

Research-grade Mod GRF (1-29) is supplied as a white lyophilised powder, usually as the acetate or trifluoroacetate salt. The molecular formula and mass in the table are calculated from the sequence; the CAS number is the one in general commercial use but we have not confirmed it against a registry entry, so a certificate should be read against the formula and mass rather than the CAS number.

How the literature describes its mechanism

Mod GRF (1-29) is an agonist at the GHRH receptor, a class B G-protein-coupled receptor expressed on the somatotroph cells of the anterior pituitary. The parent hormone was isolated in 1982 from pancreatic tumours that had caused acromegaly, by Guillemin's group at the Salk Institute and by Rivier, Vale and colleagues working with Thorner's clinical material, and sequenced as a 44-residue amidated peptide [1, 2]. Within a year Wehrenberg and Ling had shown that the N-terminal fragment GRF(1-29)-NH2 carried the full biological potency of the native hormone in rats, and that shorter fragments lost activity rapidly [3]. GRF(1-29)-NH2 became the drug sermorelin, and it is the scaffold on which every subsequent GRF analogue, including Mod GRF (1-29), is built. Receptor activation depends on the N-terminal residues, with Tyr1, Ala2 and Asp3 particularly sensitive to modification, while the C-terminal half forms an amphipathic α-helix that contributes to binding affinity [8].

Receptor occupancy by a GRF agonist raises intracellular cyclic AMP through Gs and adenylyl cyclase, which in the somatotroph drives growth hormone synthesis and release. The response is pulsatile in vivo because it is gated by hypothalamic somatostatin, and one of the more interesting findings in the CJC-1295 clinical work was that continuous receptor stimulation by the long-acting conjugate did not abolish that pulsatility: pulse amplitude and trough GH rose, but pulse frequency did not change [12]. Mod GRF (1-29) without a DAC is expected to behave like sermorelin, as a short-lived agonist; the literature on it specifically, as distinct from the conjugate or the parent hormone, is thin.

The four substitutions and why they were made. Each change in the tetrasubstituted sequence addresses a specific chemical or enzymatic liability of GRF(1-29), and the reasons are set out in the Roche group's papers [5, 6, 7, 8].

D-Ala2. Frohman and colleagues showed in 1986 that human GHRH is cleaved in plasma within minutes by dipeptidyl peptidase IV, which removes the N-terminal Tyr-Ala dipeptide to give GHRH(3-44), a product that is biologically inactive [4]. Replacing L-alanine at position 2 with D-alanine makes the Ala2-Asp3 bond a poor substrate for the enzyme. Soule, King and Millar later demonstrated in healthy men that [D-Ala2]GRF(1-29)-NH2 had a longer half-life and a lower metabolic clearance rate than the unsubstituted peptide [9]. This is the single substitution that matters most for persistence in a biological matrix.

Gln8. The native residue at position 8 is asparagine. Friedman and colleagues showed in 1991 that the dominant degradation route for GRF analogues in neutral aqueous solution is deamidation of asparagine residues [5], and Bongers and colleagues characterised the chemistry in detail the following year, including the succinimide intermediate and the formation of iso-aspartyl products at Asn8 and the isomerisation of Asp3 and Asp25 [6]. Glutamine deamidates much more slowly than asparagine, so the Gln8 substitution removes the main chemical instability of the peptide in solution.

Ala15. Position 15 is glycine in the native sequence, in the middle of the helical region. Glycine is helix-destabilising; alanine is the most helix-favouring residue. The substitution increases the helical content and the receptor affinity of the analogue [8].

Leu27. The native residue is methionine, whose thioether is readily oxidised to the sulphoxide during synthesis, purification and storage, with loss of potency. Replacing it with leucine, which is isosteric and non-oxidisable, removes that liability [7, 8].

Campbell, Bongers and Felix reviewed this design programme in 1995, including the combination of substitutions into single analogues with improved stability and potency [8]; the 1994 Peptides paper from the same group reports multiply substituted GRF analogues with enhanced plasma stability and GH-releasing potency in animals [7]. The tetrasubstituted peptide is one product of that work, and when ConjuChem selected a GRF sequence for conjugation to albumin they chose it because it had already been engineered against DPP-IV, deamidation and oxidation [10].

For an in-vitro programme, the relevant readouts are GHRH receptor binding and cyclic AMP accumulation in receptor-expressing cells, GH release from primary pituitary cells or GH-secreting cell lines, and stability in plasma or buffer. Jetté and colleagues used rat anterior pituitary cells and a GRF receptor binding assay to compare the conjugate with the unconjugated peptide [10], and that paper is a reasonable starting point for assay design.

The research record

The literature divides into three bodies that are often conflated: structure-activity work on GRF analogues from the 1980s and 1990s, the ConjuChem clinical and preclinical work on CJC-1295 with the DAC, and a small anti-doping literature. There is no published controlled human study of Mod GRF (1-29) without a DAC as such, and that should be understood before any of the following is read.

The analogue design work. The Roche papers are primarily chemistry and animal pharmacology: plasma stability, receptor binding and GH release in rats or pigs, comparing many analogues rather than characterising one [5, 6, 7, 8]. The one human study that bears directly on a single substitution is the Soule study of [D-Ala2]GRF(1-29)-NH2 in normal men, which reported a longer half-life and reduced clearance relative to the unsubstituted peptide [9]. That is the best human evidence for the principle behind the D-Ala2 substitution; it is not a study of the tetrasubstituted peptide.

CJC-1295 with DAC: preclinical. Jetté and colleagues at ConjuChem prepared a series of GRF(1-29) analogues bearing a C-terminal lysine-maleimidopropionic acid group, showed that they formed covalent conjugates with albumin, demonstrated that the conjugates still bound and activated the GRF receptor on rat anterior pituitary cells, and selected the tetrasubstituted analogue conjugate, named CJC-1295, on the basis of its sustained elevation of GH and IGF-1 in rats [10]. Alba and colleagues then showed that once-daily administration of CJC-1295 to GHRH-knockout mice, which are dwarfed because they lack the hormone, normalised growth and IGF-1 and restored pituitary GH content [13]. These are the only two primary animal papers on the conjugate of any size.

CJC-1295 with DAC: human. Teichman and colleagues reported in 2006 the combined results of two placebo-controlled phase I studies in healthy adults, one with single doses and one with repeated doses. A single administration raised mean plasma GH two- to ten-fold for six days or more and IGF-1 one-and-a-half- to three-fold for nine to eleven days; the estimated half-life was between about six and eight days; repeated administration produced cumulative increases in IGF-1; and the compound was described as well tolerated, with injection-site reactions, headache and transient flushing the most common events [11]. Ionescu and Frohman, in a separate study the same year, sampled GH frequently in healthy subjects after a single administration and showed that pulsatile GH secretion persisted during continuous stimulation, with increased pulse amplitude and basal GH but unchanged pulse frequency [12]. Sackmann-Sala and colleagues later applied two-dimensional gel proteomics to serum from the Teichman study and reported changes in a set of serum proteins, including apolipoproteins and transthyretin isoforms, consistent with activation of the GH–IGF-1 axis [14].

That is the entire peer-reviewed human record. ConjuChem's programme for CJC-1295 was aimed at HIV-associated lipodystrophy; contemporary company announcements indicate it was suspended in 2006 and never resumed, and the company has since ceased trading. No marketing application was made to any regulator and no phase III data exist. The compound has been, for nearly two decades, a discontinued investigational drug whose data set consists of a few dozen healthy volunteers.

The anti-doping literature. The persistence of the name in commerce is documented by Henninge and colleagues at the Norwegian Doping Control Laboratory, who in 2010 identified CJC-1295 by mass spectrometry in an unlabelled preparation submitted for analysis, and noted that it was being marketed despite the absence of any approved medicine containing it [15].

Taking the record as a whole. Mod GRF (1-29) is a well-reasoned piece of 1990s peptide chemistry whose substitutions each have a published rationale. It is not itself the subject of any controlled human study. The human data usually quoted in connection with it concern a different molecule, the albumin-binding conjugate, whose pharmacokinetics are dominated by the DAC and do not transfer to the unconjugated peptide. This page makes no therapeutic claim for either compound.

Regulatory status in the United Kingdom

Mod GRF (1-29) is not licensed as a medicine in the UK or anywhere else. It has no marketing authorisation, no pharmacopoeial monograph and no approved use. CJC-1295, the conjugate, is likewise unlicensed everywhere. No GHRH analogue is currently authorised by the MHRA for routine clinical use: sermorelin was once marketed in some countries as a diagnostic agent and has been withdrawn, and tesamorelin, which is approved in the United States, has no UK licence. BuyUK Peptides supplies Mod GRF (1-29) as a research chemical for in-vitro laboratory use under the Terms of Sale. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for ensuring their use of the material complies with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.

The World Anti-Doping Agency's Prohibited List, in force from 1 January 2026, lists under category S2 (peptide hormones, growth factors, related substances and mimetics) "growth hormone-releasing hormone (GHRH) and its analogues (e.g., CJC-1293, CJC-1295, sermorelin, and tesamorelin)" [16]. CJC-1295 is named explicitly, and Mod GRF (1-29) is a GHRH analogue and falls within the same entry whether or not it is named. S2 substances are prohibited at all times, in and out of competition. Any researcher whose institution is subject to anti-doping rules should be aware of this; the Henninge paper is a reminder that material under this name circulates in exactly that context [15].

Handling, storage and stability

Mod GRF (1-29) is supplied lyophilised in a glass vial with a rubber stopper and an aluminium flip-off crimp. It is a 29-residue, cysteine-free, unlipidated, amidated peptide that was specifically engineered for chemical stability, and in practice it is more robust in solution than sermorelin or the native hormone, although the published stability work concerns plasma and buffer at physiological pH rather than long-term storage of research solutions [5, 6, 7].

Sealed vial. Store at 2–8 °C for routine use and at −20 °C or below for storage beyond a few months. Protect from light. Avoid repeated freeze–thaw cycles. Allow a refrigerated vial to reach room temperature before opening, so that moisture does not condense onto the cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile bacteriostatic water, sterile water for injection, or a buffer appropriate to the assay. The peptide carries three arginines and two lysines against two aspartates, so it is net positively charged at neutral pH and dissolves readily in water. Add the solvent down the side of the vial and swirl gently; do not shake. The C-terminal half of the molecule is an amphipathic helix, so the peptide foams if agitated and adsorbs to plastic and glass at low concentration; low-binding tubes and tips are advisable for dilute working solutions. The reconstitution calculator gives the volume to add for a target concentration.

Reconstituted solution. Keep at 2–8 °C and protect from light. The Gln8 and Leu27 substitutions remove the two fastest chemical degradation routes of the parent sequence, but Asp3 and Asp25 remain and can isomerise slowly at neutral and alkaline pH [6], so a conservative practice is to use a working solution within 28 days and to discard it if it becomes cloudy. Aliquoting into single-use volumes and freezing at −20 °C is a sensible alternative. Avoid strongly alkaline buffers, which accelerate aspartate isomerisation.

Solubility. Mod GRF (1-29) acetate is freely soluble in water at research concentrations. Reference-standard suppliers describe the related conjugate as only sparingly soluble in phosphate-buffered saline, so a small volume of water or dilute acetic acid is the better first solvent, followed by dilution into the assay buffer. Where filtration is required, a 0.22 µm low-protein-binding membrane (PVDF or PES) should be used, since nylon and nitrocellulose retain a measurable fraction of an amphipathic peptide.

What a sound certificate for CJC-1295 (no DAC) looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For this compound the certificate has one job above all others: to establish that the vial contains the unconjugated tetrasubstituted peptide and not sermorelin, not a deletion sequence, and not the DAC conjugate.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. The average molecular weight of Mod GRF (1-29) is 3367.9 Da and the monoisotopic mass is approximately 3365.9 Da. A peptide of this size and charge usually appears as the [M+3H]3+ ion at about 1123.6 and the [M+4H]4+ ion at about 843.0, with a weaker [M+2H]2+ at about 1685.0, and a certificate may report any of these or a deconvoluted mass. The observed mass should agree with the theoretical value to within about 0.5 Da. Three mismatches are diagnostic. A mass of about 3357.9, ten daltons lower, indicates sermorelin (C149H246N44O42S). A mass of about 3647.3, some 279 daltons higher, indicates the DAC conjugate CJC-1295 (C165H269N47O46). A mass 16 daltons high indicates oxidation, most likely at a tyrosine. What LC-MS cannot do is distinguish D-alanine from L-alanine at position 2, because they have identical mass; that requires chiral amino acid analysis after hydrolysis, which is not routinely performed on research-grade material, and a certificate should not be read as proving it.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection at 214 or 220 nm reports purity as the area of the main peak as a percentage of all integrated peaks. A good batch shows a single dominant peak with purity of 98% or above. For a 29-mer the principal impurities are deletion sequences and incompletely deprotected side chains, which elute close to the main peak. Deamidation and aspartate isomerisation products appear as a shoulder slightly earlier than the parent, and their absence is one of the things the Gln8 substitution was designed to achieve. A certificate that shows the chromatogram is more informative than one that reports a number alone.

Net peptide content. Lyophilised peptides contain bound water and counter-ions, and for a peptide with five basic residues the trifluoroacetate or acetate fraction can be substantial. Net peptide content, where reported, expresses the fraction that is actual peptide, and it matters for preparing solutions of accurate concentration.

Endotoxin. Where the batch has been tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram. This is relevant to primary pituitary cultures, where endotoxin can alter hormone secretion and confound a GH-release readout.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

Mod GRF (1-29) is most often discussed alongside ipamorelin, a pentapeptide growth hormone secretagogue that acts at the ghrelin (GHS-R1a) receptor rather than the GHRH receptor; the in-vitro secretagogue literature includes experiments combining the two receptor inputs on the somatotroph. The other compounds in this class are sermorelin, the unsubstituted GRF(1-29)-NH2 and the direct comparator for any stability experiment on Mod GRF (1-29) [3, 5, 6], and tesamorelin, an N-acylated GRF(1-44) analogue developed independently. CJC-1295 with DAC is a different molecule, as set out above, and is not supplied under this listing.

Frequently asked questions

Is "CJC-1295 no DAC" the same as CJC-1295? No. CJC-1295 is the albumin-binding conjugate developed by ConjuChem, with a lysine-maleimidopropionic acid group at the C-terminus and a half-life of about a week in humans [10, 11]. "No DAC" material is the underlying 29-residue peptide without that group, properly called Modified GRF (1-29). All of the published human data concern the conjugate.

Is it the same as sermorelin? No, though closely related. Sermorelin is GRF(1-29)-NH2 with the native sequence. Mod GRF (1-29) has four substitutions, D-Ala2, Gln8, Ala15 and Leu27, each made to remove a specific instability [7, 8]. The two differ by 10 Da and are distinguishable by LC-MS.

Are there any human trials of the no-DAC peptide? Not of the tetrasubstituted peptide itself. There is a human pharmacokinetic study of the single D-Ala2 substitution [9], and phase I studies of the DAC conjugate [11, 12, 14]. There is no controlled trial of Mod GRF (1-29).

Is it on the WADA list? Yes. GHRH and its analogues are listed under S2, with CJC-1295 named as an example, and the entry applies at all times [16].

Can a certificate confirm the D-alanine? Not by mass spectrometry, which cannot tell D- from L-alanine. The certificate confirms mass, purity and the absence of the DAC; it does not independently confirm stereochemistry at position 2.

How long does a sealed vial last? Lyophilised peptides of this kind are stable for years at −20 °C and for many months at 2–8 °C. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Guillemin R, Brazeau P, Bohlen 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.
2. 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. doi:10.1038/300276a0.
3. Wehrenberg WB, Ling N. In vivo biological potency of rat and human growth hormone-releasing factor and fragments of human growth hormone-releasing factor. Biochemical and Biophysical Research Communications. 1983;115(2):525–530. doi:10.1016/s0006-291x(83)80176-4.
4. 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 NH2 terminus. Journal of Clinical Investigation. 1986;78(4):906–913. doi:10.1172/JCI112679.
5. Friedman AR, Ichhpurani AK, Brown DM, et al. Degradation of growth hormone releasing factor analogs in neutral aqueous solution is related to deamidation of asparagine residues. International Journal of Peptide and Protein Research. 1991;37(1):14–20. doi:10.1111/j.1399-3011.1991.tb00727.x.
6. Bongers J, Heimer EP, Lambros T, Pan YCE, Campbell RM, Felix AM. Degradation of aspartic acid and asparagine residues in human growth hormone-releasing factor. International Journal of Peptide and Protein Research. 1992;39(4):364–374. doi:10.1111/j.1399-3011.1992.tb01596.x.
7. Campbell RM, Stricker P, Miller R, et al. Enhanced stability and potency of novel growth hormone-releasing factor (GRF) analogues derived from rodent and human GRF sequences. Peptides. 1994;15(3):489–495. doi:10.1016/0196-9781(94)90211-9.
8. Campbell RM, Bongers J, Felix AM. Rational design, synthesis, and biological evaluation of novel growth hormone releasing factor analogues. Biopolymers. 1995;37(2):67–88. doi:10.1002/bip.360370204.
9. Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. The Journal of Clinical Endocrinology & Metabolism. 1994;79(4):1208–1211. doi:10.1210/jcem.79.4.7962295.
10. 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. doi:10.1210/en.2004-1286.
11. 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. The Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799–805. doi:10.1210/jc.2005-1536.
12. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. The Journal of Clinical Endocrinology & Metabolism. 2006;91(12):4792–4797. doi:10.1210/jc.2006-1702.
13. Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American Journal of Physiology-Endocrinology and Metabolism. 2006;291(6):E1290–E1294. doi:10.1152/ajpendo.00201.2006.
14. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Hormone & IGF Research. 2009;19(6):471–477. doi:10.1016/j.ghir.2009.03.001.
15. Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Testing and Analysis. 2010;2(11-12):647–650. doi:10.1002/dta.233.
16. World Anti-Doping Agency. The Prohibited List 2026, section S2.4, growth hormone-releasing factors. In force 1 January 2026. wada-ama.org/en/prohibited-list.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.