CJC-1295 and ipamorelin act on different receptors. CJC-1295 is a modified version of GHRH(1-29) that activates the GHRH receptor, while ipamorelin is a five-residue peptide that activates the ghrelin receptor, GHS-R1a. "CJC-1295" itself comes in two forms: with DAC, where a reactive lysine lets the peptide bond covalently to serum albumin, and without DAC, also called modified GRF(1-29), which is the same 29-residue peptide with no albumin-binding group.
This post untangles the naming, sets out the four amino acid substitutions and the DAC chemistry with their sources, and compares both forms of CJC-1295 with ipamorelin.
The naming problem
The name CJC-1295 is used loosely, and it causes real confusion when ordering and when reading the literature.
- CJC-1295 (the original compound). In the 2005 paper that introduced it, Jetté and colleagues at ConjuChem defined CJC-1295 as a tetrasubstituted form of hGRF(1-29) with an added lysine at the C-terminus carrying an N-epsilon-3-maleimidopropionamide group. That reactive group is what is now called the Drug Affinity Complex, or DAC. The PubChem record for CJC-1295 (CID 91971820) describes this molecule.
- CJC-1295 without DAC. The same tetrasubstituted GRF(1-29) amide, with no extra lysine and no maleimide. It is sold as "CJC-1295 no DAC", "modified GRF(1-29)" or "mod GRF 1-29". These are one molecule under several names.
- Sermorelin. The unmodified GHRH(1-29) amide that both forms were derived from. We compare it with ipamorelin in Sermorelin vs Ipamorelin.
In the primary literature, "CJC-1295" without qualification means the DAC form. Anhydrolabs lists the no-DAC form, under the name CJC-1295 (no DAC).
The four substitutions
Both forms of CJC-1295 share the same 29-residue backbone. Compared with native GHRH(1-29)NH2, four residues are changed. We confirmed each position by reading the full systematic name of CID 91971820 in PubChem residue by residue against the sermorelin sequence.
| Position | Native GHRH(1-29) | CJC-1295 backbone | What the change does chemically |
|---|---|---|---|
| 2 | L-Ala | D-Ala | Alters the Tyr1-Ala2 site that plasma dipeptidyl peptidase (DPP-4) cleaves |
| 8 | Asn | Gln | Replaces an asparagine followed by serine, a sequence motif prone to deamidation |
| 15 | Gly | Ala | Replaces glycine, the most flexible residue and a weak helix former, with alanine, a strong helix former |
| 27 | Met | Leu | Removes the only methionine, which can oxidize to methionine sulfoxide |
The position 2 change addresses the best-documented weakness of GHRH. Frohman and colleagues showed in 1986 that plasma removes the N-terminal Tyr-Ala dipeptide of GHRH, leaving GRH(3-44), which has less than a thousandth of the original activity. Jetté and colleagues reported that their albumin conjugates were more stable against DPP-4 in vitro than the parent peptide.
The other three changes remove chemically labile or conformationally weak points. The Met27 swap is easy to check in the data: PubChem gives CJC-1295 the formula C165H269N47O46, which contains no sulfur, whereas sermorelin (C149H246N44O42S) has one sulfur atom, from Met27.
What the DAC is
"DAC" stands for Drug Affinity Complex, ConjuChem's name for its albumin-binding technology. In CJC-1295 it consists of two parts:
- An extra lysine at position 30, added after Arg29, with a C-terminal amide.
- A 3-maleimidopropionyl group attached to that lysine's side-chain (epsilon) amine.
A maleimide reacts rapidly and selectively with free thiol groups to form a stable thioether bond. Serum albumin has one free thiol, on cysteine 34. Jetté and colleagues designed CJC-1295 to find that thiol after entering the circulation and attach to albumin covalently, in what they called in vivo bioconjugation. In their rat studies, a CJC-1295 immunoreactive species appeared on the serum albumin band of a Western blot within 15 minutes and remained beyond 24 hours, and the compound was present in plasma beyond 72 hours.
Albumin is large (about 66.5 kDa) and long-lived in circulation, so a peptide attached to it inherits much of that persistence. In a 2006 human study of the DAC form, Teichman and colleagues estimated the half-life of CJC-1295 at 5.8 to 8.1 days. For comparison, Frohman measured the half-life of intact native GHRH(1-44) after intravenous delivery at 6.8 minutes.
CJC-1295 with DAC vs without DAC
| Property | CJC-1295 with DAC | CJC-1295 without DAC (mod GRF 1-29) |
|---|---|---|
| Length | 30 residues (29 + Lys30) | 29 residues |
| Substitutions vs GHRH(1-29) | D-Ala2, Gln8, Ala15, Leu27 | D-Ala2, Gln8, Ala15, Leu27 |
| C-terminal group | Lys(ε-3-maleimidopropionyl)-NH2 | Arg29-NH2 |
| Molecular formula | C165H269N47O46 (PubChem) | C152H252N44O42 (calculated) |
| Molecular weight | 3,647.2 g/mol (PubChem) | About 3,367.9 g/mol (calculated) |
| PubChem CID | 91971820 | No dedicated record at the time of writing |
| CAS number | 446262-90-4 | Not assigned in PubChem |
| Reactive toward thiols | Yes (maleimide) | No |
| Albumin binding | Covalent, to Cys34 | None by design |
| Reported half-life | 5.8–8.1 days in humans (Teichman, 2006) | Not established in a peer-reviewed study we could verify |
We calculated the no-DAC formula from the sequence: sermorelin's formula, plus one CH2 each for Asn8 to Gln8 and Gly15 to Ala15, and the Met27 to Leu27 exchange (adding one carbon and two hydrogens, removing the sulfur). Adding back the lysine and the maleimidopropionyl group reproduces PubChem's formula for the DAC form exactly, which is a useful cross-check.
The roughly 279 Da difference between the two forms is easy to see by mass spectrometry, which makes MS the quickest way to confirm which one a vial contains. Our guide on how to read a peptide certificate of analysis covers what the mass entry on a certificate should show.
We have not found a peer-reviewed half-life for the no-DAC form, and we do not quote the figures that circulate online for it.
CJC-1295 vs ipamorelin
With the CJC-1295 forms sorted out, the comparison with ipamorelin is a comparison of two receptor systems.
| Feature | CJC-1295 (either form) | Ipamorelin |
|---|---|---|
| Class | GHRH analog | Ghrelin receptor agonist (GHRP family) |
| Sequence | Y-(D-A)-DAIFTQSYRKVLAQLSARKLLQDILSR-NH2 (+ Lys-DAC in the DAC form) | Aib-His-D-2-Nal-D-Phe-Lys-NH2 |
| Length | 29 or 30 residues | 5 residues |
| Molecular weight | About 3,368 or 3,647 g/mol | 711.9 g/mol |
| Receptor | GHRH receptor (class B GPCR) | GHS-R1a (class A GPCR) |
| Main signaling | Gs, adenylyl cyclase, cyclic AMP | Gq/11, phospholipase C, IP3 and calcium |
| Developer | ConjuChem (Montreal) | Novo Nordisk (Denmark) |
| First described | 2005 | 1998 |
| Regulatory status | Investigational; never approved | Investigational; never approved; Phase 2 study completed |
The GHRH receptor side
The GHRH receptor is a class B GPCR that UniProt describes as coupled to G proteins that activate adenylyl cyclase, stimulating somatotroph growth, growth hormone gene transcription and growth hormone secretion. CJC-1295 keeps the native residue identities at the N-terminus that switch this receptor on, changing only the configuration of Ala2. In the Jetté study, CJC-1295 was active in a growth hormone secretion assay in cultured rat anterior pituitary cells.
The ghrelin receptor side
Ipamorelin works through the ghrelin receptor, GHS-R1a, which couples to Gq and drives phospholipase C, IP3 and calcium signaling. In the 1998 study that introduced it, Raun and colleagues used GHRP and GHRH antagonists to show that ipamorelin acts through the GHRP receptor, not the GHRH receptor. In swine, ipamorelin did not raise ACTH or cortisol above the levels seen with GHRH, unlike GHRP-6 and GHRP-2, and none of the compounds changed FSH, LH, prolactin or TSH.
Why the two appear together
Because CJC-1295 and ipamorelin reach the somatotroph through separate receptors and separate second messengers, they give researchers two independent handles on growth hormone secretion. Receptor antagonists, as in the Raun study, can then assign a response to one pathway or the other. That independence is also why the two are commonly supplied side by side, and why Anhydrolabs lists a two-component lyophilized blend, Ipamorelin / CJC-1295 (no DAC), alongside the single compounds. We make no claim about how the combination behaves in any organism.
Where both sit among growth hormone secretagogues
Both compounds are growth hormone secretagogues: each is a peptide that can stimulate growth hormone release from the somatotroph cells of the pituitary gland, as opposed to supplying the hormone itself. They approach that cell from opposite sides. CJC-1295 copies growth hormone-releasing hormone, the hypothalamic peptide. Ipamorelin is a growth hormone secretagogue of the ghrelin-mimetic type, one of the GH secretagogues descended from the GHRP series. In both cases any GH release is endogenous growth hormone from the pituitary's own growth hormone production.
The long-lived DAC form raised a specific question: would continuous stimulation of the GHRH receptor flatten the normal pulsatile pattern of secretion? Ionescu and Frohman examined this in 2006, sampling blood every 20 minutes overnight in men before and one week after CJC-1295. They reported that pulsatility was preserved, so that each GH pulse remained distinguishable.
Tesamorelin is the GHRH analog most often named beside these two. PubChem describes it as a stabilized synthetic peptide analogue of GHRH (C221H366N72O67S, about 5,136 g/mol). Of the three it is the only one with an FDA-approved product, for a specific indication in HIV-associated lipodystrophy, and it is a different molecule from either form of CJC-1295.
Regulatory status
Neither form of CJC-1295 has been approved by the FDA or, to our knowledge, any other regulator. The DAC form was studied in healthy adults in two randomized, placebo-controlled trials reported in 2006, which measured growth hormone and IGF-I concentrations and the compound's pharmacokinetics.
Ipamorelin is also investigational. Its most advanced published study was a Phase 2 trial in postoperative ileus after bowel resection (ClinicalTrials.gov NCT00672074), reported by Beck and colleagues in 2014.
Anhydrolabs supplies these compounds as research reagents, not for human or veterinary diagnosis, treatment, or consumption. The terms are on our research-use page.
Handling notes
- The DAC form is thiol-reactive. A maleimide will react with any free thiol in solution, including dithiothreitol, 2-mercaptoethanol, glutathione, cysteine or thiol-containing proteins in a medium. Maleimides also hydrolyze slowly in water, faster at higher pH. Keep that in mind when choosing buffers.
- The no-DAC form is less reactive, with no methionine or cysteine, and handles like other mid-sized linear peptides.
- Ipamorelin is small, contains no methionine or cysteine, and is usually supplied as the acetate salt.
- Reconstitution and storage. All three ship as lyophilized powders. See how to reconstitute peptides and the storage and handling page.
For the downstream end of this axis, our profile of IGF-1 LR3 covers an engineered IGF-1 analog that acts on the IGF-1 receptor directly.
Anhydrolabs supplies ipamorelin, CJC-1295 (no DAC) and the blend as lyophilized powders in vacuum-sealed vials, also available as 10-vial kits.
