Molecule guides
What Is CJC-1295 with DAC? Albumin Conjugation, GHRH Receptor Pharmacology and Research Use
The long-acting GHRH analogue explained: how its maleimide linker latches onto albumin Cys34, what days-long receptor occupancy changes, and how to handle and verify the material.
Key facts
- CAS number: 863288-34-0
- Molecular formula: C165H269N47O46
- Molecular weight: 3647.28 g/mol
- Purity: ≥99% by HPLC; lot-matched COA available
- Form: Lyophilized powder, sealed glass vial
- Storage: −20 °C, sealed and protected from light and moisture
- Available sizes: 2 mg · 5 mg · 10 mg
CJC-1295 with DAC is Modified GRF 1-29 extended by one lysine at position 30, and that lysine carries a maleimidopropionyl group known as the drug affinity complex (DAC). Once in plasma, the group forms a permanent bond to the thiol of cysteine-34 on serum albumin, so a peptide that would otherwise be gone in minutes stays in circulation for days. That chemistry is the whole story. Every property that sets it apart from plain CJC-1295 (the unconjugated peptide) comes from this one reactive group. Its research role follows: it is chosen when an experiment needs the GHRH receptor occupied continuously, not briefly.
This guide explains the conjugation chemistry, how the peptide acts at its receptor, what continuous exposure changes, and how the research material is specified and handled.
Design and structure: how the DAC linker works
Albumin is almost tailor-made for this job. No plasma protein is more abundant; each molecule lasts around three weeks before it is turned over; and of all its cysteines, only Cys34 is left unpaired with a reactive thiol. A small peptide that latches onto that one site borrows the carrier's longevity — the entire premise of the DAC approach.
Maleimides combine with thiols through Michael addition to give a stable thioether linkage, and at near-neutral pH they do so highly selectively. A peptide carrying a maleimidopropionyl group will therefore seek out and bind albumin's Cys34 once it enters the circulation. The resulting conjugate is much too large to be filtered by the kidneys and is protected from most peptidases, so its clearance tracks albumin turnover rather than that of the peptide.
The placement matters. The maleimide is attached to the added lysine at position 30, past the C-terminus of the receptor-binding 1–29 segment, so the reactive group sits as far as possible from the residues that touch the receptor. The backbone underneath is Modified GRF 1-29, with D-Ala2, Gln8, Ala15 and Leu27 substitutions; the DAC version therefore inherits all of that analogue's chemical stability and adds albumin binding on top. The masses show it clearly — 3647.28 g/mol with DAC against 3367.93 g/mol without, a difference of roughly 279 Da made up by the extra lysine and the linker.
Mechanism of action
Receptor pharmacology is the same as for any GHRH analogue. The peptide binds GHRH receptors on somatotroph cells of the pituitary, activating Gs; cAMP rises, protein kinase A is switched on, and growth hormone synthesis and release increase.
The difference lies in how long the receptor is exposed. Native GHRH and sermorelin produce a peak that lasts minutes, Modified GRF 1-29 a somewhat longer pulse, and the albumin-conjugated peptide a plateau lasting days — animal studies and early human pharmacokinetic data from its development reported half-lives of several days. Pharmacologically that is a different experiment altogether, and the published literature spells out the consequences. Sustained agonist binding at a class B GPCR tends to desensitise and downregulate the receptor, and it removes the pulsatile pattern that characterises the normal GH axis.
For research purposes, that is the point. To study what continuous GHRH receptor stimulation does to somatotroph signalling, receptor levels or IGF-1 further downstream, you need a long-acting agonist; a short-acting one is the wrong tool. For pulsatile physiology it is the reverse. Picking a form is a study-design decision, not a preference, and CJC-1295 vs CJC-1295 with DAC sets out the trade-offs.
Research applications
Pharmacokinetics and sustained receptor occupancy
Animal and early-phase human pharmacokinetic studies from the original development programme confirmed the multi-day persistence that DAC conjugation was designed to deliver, and reported sustained rises in growth hormone and IGF-1 markers. Development stopped before approval; no CJC-1295 product holds a marketing authorisation anywhere.
Receptor desensitisation and axis regulation
Whether an agonist is delivered steadily or in bursts changes receptor behaviour throughout the class B GPCR family, and a GHRH analogue that lingers for days is a convenient way to test that. Typical measurements are receptor abundance, how strongly cAMP responds when cells are stimulated a second time, and what happens to IGF-1 downstream.
Comparative structure–activity studies
With and without DAC, the two peptides are identical except for one structural element. That makes them an unusually clean pair: any difference in outcome can be put down to how long the receptor was exposed, since the receptor pharmacology itself is the same — a degree of control rarely available in peptide work.
Combination designs
Many protocols combine a GHRH-side agonist with one acting at the ghrelin-receptor (GHS-R1a) agonist site, ipamorelin being the usual choice; the two targets share the somatotroph but signal through different second messengers. A ready-mixed research product is sold as CJC-1295 DAC with ipamorelin. Be aware that a long-lived partner plus a short-lived one gives an exposure curve more complex than either on its own, and write that into the methods.
Available formats and vial sizes
CJC-1295 with DAC is supplied freeze-dried in sealed vials: 2 mg (USD 55), 5 mg (USD 100) and 10 mg (USD 180). With a molecular weight of 3647.28 g/mol, 5 mg is roughly 1.37 micromoles, slightly below the 1.48 micromoles in 5 mg of the non-DAC version — remember this when matching the two on a molar basis. Both appear under GHRH analogs.
Reconstitution and storage at the bench
Example: a 5 mg vial dissolved in 2 mL of bacteriostatic water gives 2.5 mg/mL (2,500 mcg/mL); 0.1 mL, i.e. 10 units on a U-100 scale, then contains 250 mcg. Expressed as molarity, the stock is about 686 micromolar.
One handling point is specific to this peptide and matters more than any other. The maleimide will react with any free thiol it meets, not only albumin's. Reducing agents in buffers or diluents — DTT, β-mercaptoethanol — will consume it, and so will free cysteine or thiol-containing additives in cell-culture media. Maleimides also slowly hydrolyse in water, more quickly at alkaline pH, gradually losing their ability to conjugate. So: reconstitute in a thiol-free diluent close to neutral pH, keep solution time short, and freeze aliquots. Unopened vials belong at −20 °C or colder, dry and dark. General guidance is in our peptide storage guide.
Purity and reading the certificate of analysis
We purify every lot to 99% or more by reversed-phase HPLC, confirm its mass and issue a lot-specific certificate. Of all the entries on it, the mass decides the question. You want 3647.28 g/mol. A figure around 3367.93 g/mol means you have the non-DAC peptide — and because the DAC form is the pricier of the two, that substitution should be actively ruled out. A value sitting 18 Da high tells you the maleimide ring has hydrolysed to maleamic acid; such a peptide still activates the receptor yet cannot couple to albumin, and no purity percentage will flag it. The remaining checks are routine: one symmetrical main peak, a lot number that agrees with the vial, and net peptide content compared with gross weight, as our COA reading guide explains.
Regulatory position
Neither form of CJC-1295 is authorised as a medicine in the EU, the United States or any other market; development ended before approval. It is not a permitted food supplement ingredient and not a routinely available compounded medicine. We supply it for laboratory research only, not for human consumption.
Related compounds and further reading
For experiments that isolate exposure time, the non-DAC version — its exact structural twin — is the right comparator. Sermorelin is the unmodified 1–29 parent, and tesamorelin the lipidated full-length analogue. Ipamorelin and the GHRP family work on the other side of the axis, at the ghrelin receptor instead of the GHRH receptor; see the GH secretagogue landscape explained for how all of these relate.
Matching catalogue section: GHRH Analogs
Questions
What does "DAC" mean in CJC-1295 with DAC?
Drug affinity complex: a maleimidopropionyl group on an additional lysine at position 30, just beyond the 1 to 29 receptor-binding segment. Via a Michael addition, that maleimide couples to the thiol of Cys34 on circulating albumin, and the resulting thioether is stable — effectively chaining the peptide to a protein that survives for weeks.
Why does binding to albumin lengthen the half-life so dramatically?
Albumin is plasma's most abundant protein and circulates for roughly three weeks. Once the peptide is bound to it, the complex is too big for the kidneys to filter and is largely shielded from peptidases, so it is removed at albumin's turnover rate instead of a peptide's. Animal and early human pharmacokinetic studies reported half-lives of several days.
How does CJC-1295 with DAC differ from CJC-1295 without DAC?
Backbone and receptor action are identical: both are Modified GRF 1-29 analogues acting at the GHRH receptor. The DAC version simply adds a lysine at position 30 carrying the maleimide linker, so it weighs 3647.28 rather than 3367.93 g/mol. What changes in practice is exposure — several days of steady occupancy versus a pulse that is over in much less than an hour.
In which studies is the DAC version the right choice?
Studies needing uninterrupted GHRH receptor occupancy — for example, how prolonged agonist exposure changes somatotroph signalling, receptor levels, desensitisation and downstream IGF-1. For pulsatile physiology or discrete receptor stimulation, the short-acting non-DAC form is the right choice. The decision follows from the design, not from preference.
Can the maleimide react with things other than albumin?
Yes, and this is the main handling hazard. A maleimide reacts with whatever free thiol is available, so DTT, β-mercaptoethanol, free cysteine or thiol-containing culture supplements will all use up the linker. Reconstitute in a thiol-free diluent close to neutral pH and keep the peptide in solution for as short a time as possible.
What is maleamic acid, and why should researchers care?
Maleamic acid is the product of maleimide ring hydrolysis, a slow process in water that speeds up at alkaline pH. On a mass spectrum it appears 18 Da heavier than expected. The hydrolysed peptide still activates the GHRH receptor but cannot bind albumin any more, so its long action is lost — and the purity figure will not show it.
Which check on a CJC-1295 with DAC certificate matters most?
The measured mass, which should be 3647.28 g/mol. A value near 3367.93 g/mol indicates the non-DAC peptide, a considerably cheaper product, so this possible substitution should be verified rather than assumed. A mass 18 Da above the expected figure points to a hydrolysed maleimide that cannot conjugate.
Is CJC-1295 with DAC approved as a medicine?
No. Development was halted before approval, and no CJC-1295 product holds a marketing authorisation in the United States, the EU or elsewhere. It is not a food supplement ingredient and not a routinely available compounded medicine.