CJC-1295 With and Without DAC: What's the Actual Difference?

Plain-English answer up front: CJC-1295 with DAC and CJC-1295 without DAC share the same 29-amino-acid backbone. The only structural difference is one extra residue glued to the C-terminus of the DAC version — a chemical handle that lets the peptide latch onto albumin in the bloodstream. That single addition is what stretches the half-life from a few minutes to several days. Everything below is for research use only.

If you're reading research on CJC-1295, you've probably noticed that the two names show up almost interchangeably in product listings. "CJC-1295 with DAC." "CJC-1295 without DAC." Sometimes "Modified GRF (1-29)." The naming is technically sloppy, and it matters — because chemically, the CJC-1295 DAC vs no DAC difference isn't a question of strength or potency. It's a question of how long the molecule survives in plasma, and that comes down to a single C-terminal modification.

The walk-through below covers the parent molecule (GHRH and sermorelin), the four backbone substitutions both versions share, what the "DAC" actually is at the chemistry level, and what the published pharmacokinetic numbers look like — minutes for one, days for the other. By the end you'll understand exactly what changes when you bolt a drug affinity complex onto a peptide, and what that single change does to the molecule's behavior in research models.

The Parent Molecule — GHRH and Why Half-Life Matters

Growth hormone-releasing hormone (GHRH) is a 44-residue hypothalamic peptide. When the hypothalamus signals the anterior pituitary, GHRH binds to the GHRH receptor on somatotroph cells and prompts them to release growth hormone (GH). It's one of the cleaner regulatory circuits in endocrinology: small peptide signal, well-defined receptor, measurable downstream effect.

In the early 1980s, researchers worked out that the first 29 residues of GHRH carry essentially all the receptor-activating activity of the full 44-residue molecule. That fragment became known as GRF (1-29) — sermorelin, the shortest fully functional form of the natural peptide.

Sermorelin solved the size problem but not the durability problem. Native GRF (1-29) has a plasma half-life of roughly 5 to 10 minutes. In plasma, the peptide is cleaved very rapidly at the N-terminus by dipeptidyl peptidase-4 (DPP-4), an enzyme that snips off the first two amino acids and leaves an inactive fragment behind. That short window is the single biggest pharmacological constraint on the entire GHRH family of peptides.

Every long-acting GHRH analog ever designed — sermorelin replacements, tesamorelin, the CJC series — is engineered around the same problem: keep the molecule intact long enough for the receptor activity to matter. CJC-1295, in both its forms, is a particularly clean example of that engineering. The two versions let you isolate exactly what each piece of the modification contributes.

The Shared Backbone — Tetrasubstituted GRF (1-29)

Both CJC-1295 with DAC and CJC-1295 without DAC are built on the same 29-residue scaffold called tetrasubstituted GRF (1-29). The "tetra" refers to four amino-acid changes from the sermorelin sequence:

• Position 2: L-alanine swapped for D-alanine. This inverts the stereochemistry of the peptide bond between residue 2 and aspartic acid at position 3 — the exact bond that DPP-4 normally cleaves. The enzyme can't process the D-configuration efficiently, so the N-terminus survives longer.
• Position 8: asparagine to glutamine, reducing deamidation susceptibility.
• Position 15: glycine to alanine.
• Position 27: methionine to leucine, removing an oxidation-prone residue.

All four substitutions are present in both molecules, identically. They're the chemistry that pushes the plasma half-life of the un-extended peptide from sermorelin's ~5 minutes up to at least ~30 minutes. That ~30-minute figure is the half-life of "CJC-1295 without DAC" — same compound as Modified GRF (1-29) and tetrasubstituted GRF (1-29). All three names point at the same molecule.

For another example of how small backbone substitutions reshape a peptide's behavior, see the structural chemistry of another research peptide.

If you look the two molecules up in the U.S. National Library of Medicine's PubChem database, you'll find separate records. CJC-1295 without DAC carries the molecular formula C152H252N44O42. CJC-1295 with DAC carries C165H269N47O46 and a molar mass of about 3,647 Da. The roughly 440-Dalton mass difference is the entire DAC modification: one extra residue and the reactive group attached to it.

What the DAC Actually Is

"DAC" stands for "drug affinity complex." The original ConjuChem Biotechnologies team coined the term to describe a class of half-life-extension chemistry that targets endogenous serum albumin. In CJC-1295 specifically, the DAC modification is one chemical addition: a 30th residue — lysine — appended to the C-terminus, carrying an Nε-3-maleimidopropionamide group on its side chain.

The chemistry is neat. Maleimide is a small five-membered ring that reacts selectively with free thiol groups. Human serum albumin has exactly one available free thiol — cysteine-34 (Cys34) — sitting in an accessible position on the protein's surface. When CJC-1295 enters plasma, the maleimide warhead finds that Cys34 thiol and forms a stable, covalent thioether bond. The peptide is now permanently attached to albumin.

Albumin is the most abundant protein in human plasma, present at roughly 35 to 50 grams per liter, and it has its own plasma half-life of about 19 days. By covalently tethering itself to albumin, CJC-1295 with DAC effectively inherits a fraction of that long circulation time. For a deeper look at how small structural changes alter peptide behavior, see how small structural changes alter peptide behavior.

The 2005 paper from Jetté and colleagues at ConjuChem demonstrated the conjugation directly. They synthesized three maleimido-modified GRF (1-29) derivatives, conjugated them to human serum albumin ex vivo, and showed that all three retained activity at the GH-releasing factor receptor in cultured rat anterior pituitary cells. In rats receiving the lead compound (CJC-1295), Western blot analysis of plasma showed CJC-1295 immunoreactivity on the albumin band starting 15 minutes after delivery and persisting beyond 24 hours.

That covalent-attachment strategy is what distinguishes CJC-1295's DAC from non-covalent strategies like PEGylation or fatty-acid acylation. Many half-life extenders increase persistence through size or hydrophobic binding. CJC-1295 with DAC forms an irreversible chemical bond with an endogenous protein that's already optimized for long plasma persistence.

Pharmacokinetic Side-by-Side — Minutes Versus Days

Here's where the two molecules diverge cleanly in research data:

• Sermorelin (native GRF 1-29): plasma half-life ~5–10 minutes.
• CJC-1295 without DAC (Modified GRF 1-29, tetrasubstituted): at least ~30 minutes in human plasma, sometimes longer in animal-model work.
• CJC-1295 with DAC: estimated 5.8 to 8.1 days in healthy adults.

Those CJC-1295-with-DAC numbers come from Teichman and colleagues, 2006, the first-in-human trial published in the Journal of Clinical Endocrinology and Metabolism. In two ascending-amount, placebo-controlled, double-blind studies, healthy adults aged 21 to 61 received single or repeated rounds of CJC-1295. After a single round, plasma GH levels rose 2- to 10-fold for at least 6 days, and IGF-1 levels rose 1.5- to 3-fold for 9 to 11 days. With multiple rounds, IGF-1 elevation persisted up to 28 days — a cumulative-effect pattern consistent with the multi-day half-life.

For research purposes, the two versions read differently in any pharmacology paper. The no-DAC form supports short-window experiments where transient GHRH receptor activation is the goal. The DAC form is the long-acting variant used in multi-week protocols where sustained GH and IGF-1 elevation is the experimental endpoint. They aren't interchangeable in a research context, even though the active receptor-binding chemistry is identical.

Pulsatility Preserved — A Specific Pharmacology Note

One of the more biologically interesting features of CJC-1295 with DAC: despite producing sustained receptor activation, it doesn't flatten the natural pulsatile pattern of growth hormone release. In a 2006 study by Ionescu and Frohman, healthy adult men received a single round of CJC-1295 at either 60 or 90 µg per kilogram of body weight. GH was sampled every 20 minutes over a 12-hour overnight window, before treatment and one week later.

The results were specific. Trough (baseline) GH levels increased about 7.5-fold (P < 0.0001). Mean GH increased about 46% (P < 0.01), and IGF-1 about 45% (P < 0.001). But the frequency and magnitude of the GH secretory pulses themselves were statistically unchanged. The somatotrophs were still pulsing on roughly the same rhythm. CJC-1295 just lifted the floor between pulses.

That matters scientifically because continuous GHRH receptor occupancy might be expected to desensitize the receptor and abolish pulsatility — which would be a problem, since pulsatile GH release is itself thought to be important for many downstream effects. The Ionescu-Frohman result suggested that CJC-1295 with DAC produces a sustained pharmacology without erasing the natural rhythm. That's not the typical outcome with chronic receptor stimulation, and it's part of why the molecule kept attracting endocrinology researchers even after the clinical program ended.

Animal-Model Evidence for the Sustained Action

The pharmacokinetic story holds up in animal models. In a 2006 paper from Johns Hopkins, Alba and colleagues studied GHRH-knockout (GHRHKO) mice — animals with no endogenous GHRH and stunted growth. Three groups of one-week-old GHRHKO mice were treated with 2 µg of CJC-1295 at intervals of every 24, 48, and 72 hours for five weeks.

The 24-hour-interval group reached normal body weight and length. The 48- and 72-hour groups grew significantly more than placebo-treated controls but didn't fully normalize. Pituitary RNA and GH mRNA both increased, and immunohistochemistry confirmed that somatotroph cells had proliferated under sustained GHRH receptor activation. The Alba paper is one of the cleanest demonstrations that the DAC-extended half-life translates into sustained pharmacodynamic action — and that the 24-hour interval was sufficient for full rescue in this model, while longer intervals were not.

Clinical History and Where Things Stand Today

CJC-1295 was developed by ConjuChem Biotechnologies as a candidate therapy for lipodystrophy and growth hormone deficiency. It progressed through phase I and into phase II clinical trials. In 2006, one trial participant died. The attending physician concluded that the cause was an asymptomatic coronary artery disease with plaque rupture and occlusion, judged unrelated to the study compound. The program was nonetheless halted as a precaution, and was not resumed.

CJC-1295 has never been an FDA-approved medicine. References to it today live in the research literature: pharmacology papers, anti-doping detection methods, peptide-chemistry textbooks, chemistry databases like PubChem. It is sold by chemical suppliers, including Optides, exclusively as a research reagent. It is not a pharmaceutical product, and the name "CJC-1295" on a research-grade peptide vial does not refer to a regulated therapeutic.

Frequently Asked Questions

Is CJC-1295 the same peptide as Modified GRF (1-29)?

No — but they share the same 29-amino-acid backbone. Modified GRF (1-29) is the tetrasubstituted GHRH(1-29) analogue without any C-terminal extension. CJC-1295 is the same backbone with an extra residue at the end — an Nε-maleimidopropionyl-lysine — that lets it bind albumin in plasma. The chemical names are sometimes used interchangeably in marketing materials, which is technically incorrect, and the U.S. National Library of Medicine's PubChem maintains separate records for each compound.

Why does the DAC version have such a longer half-life?

The maleimide group on the C-terminal lysine of CJC-1295 reacts with the single free thiol on cysteine-34 of human serum albumin, forming a stable covalent bond. Albumin is the most abundant protein in human plasma with a circulating half-life of about 19 days. By tethering itself to albumin, CJC-1295 with DAC effectively inherits a fraction of that long circulation time. Published estimates land in the 5.8 to 8.1 day range in healthy adults, compared with at least roughly 30 minutes for the un-extended Modified GRF (1-29) and only 5 to 10 minutes for the parent sermorelin.

Does the DAC version flatten the natural pulse pattern of growth hormone?

In a 2006 study by Ionescu and Frohman in the Journal of Clinical Endocrinology and Metabolism, a single round of CJC-1295 in healthy adult men raised trough growth hormone levels about 7.5-fold while leaving GH pulse frequency and pulse magnitude statistically unchanged. The long-acting analog elevated the floor without smoothing out the natural rhythm of pulses. That pulsatility-preserving behavior is one of the more biologically interesting features of the molecule from a research standpoint, and it distinguishes CJC-1295 from compounds that produce a flatter, sustained-release profile.

Was CJC-1295 ever an approved drug?

No. CJC-1295 (the DAC-bearing form) was developed by ConjuChem Biotechnologies and entered phase II clinical trials for lipodystrophy and growth hormone deficiency. Development was halted in 2006 after a trial participant died; the attending physician concluded that the cause was asymptomatic coronary artery disease unrelated to the study compound, but the program was discontinued as a precaution. CJC-1295 was never marketed as an FDA-approved medicine, and any reference material a researcher encounters sits in the research-literature record rather than on a drug label.

Conclusion

The CJC-1295 with-DAC versus without-DAC distinction is, at the molecular level, almost embarrassingly simple. Both molecules carry the same 29-amino-acid tetrasubstituted GRF (1-29) backbone, with the same four engineered substitutions at positions 2, 8, 15, and 27. The only difference is one C-terminal residue — Nε-maleimidopropionyl-lysine — that lets the DAC version covalently bond to albumin's Cys34 in plasma. That single extra residue is the entire reason the half-life jumps from minutes to days.

Both compounds are research reagents — neither is approved for human or animal use. If you want context on what "research-grade" actually means as a product category, see what "research-grade" actually means for a peptide product.

For research use only. Not for human or animal consumption of any kind. The information in this article is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. The statements made have not been evaluated by the U.S. Food and Drug Administration. These products are NOT FDA APPROVED. Please consult with a licensed healthcare professional before making any decisions regarding your health or research.

Optides LLC is a chemical supplier. Optides LLC is not a compounding pharmacy or chemical compounding facility as defined under 503A of the Federal Food, Drug, and Cosmetic Act. Optides LLC is not an outsourcing facility as defined under 503B of the Federal Food, Drug, and Cosmetic Act.