CJC-1295 with and without DAC: two different molecules behind one name, and what the published research actually tested

CJC-1295 with and without DAC: why one name covers two molecules#

When a research supplier lists "CJC-1295 without DAC" or "CJC-1295 no DAC", it is selling a 29-amino-acid peptide also known as modified GRF (1-29), mod GRF 1-29 or tetrasubstituted GRF (1-29). When a scientific paper, a regulator or a chemical registry uses the bare name "CJC-1295", it almost always means a different, larger molecule: the same 29-residue peptide with an extra lysine at the end carrying a chemical group that attaches the peptide to albumin in blood. That attachment system is what "DAC" (Drug Affinity Complex) refers to.

The difference is not a matter of formulation or purity. The two are distinct chemical entities with different masses, different behaviour in the studies that exist, and different entries in the registries. Results reported for one cannot be carried over to the other. The rest of this page traces both molecules back to the natural hormone they are built from.

From GHRH(1-44) to sermorelin to modified GRF (1-29)#

Growth hormone-releasing hormone (GHRH, also written GRF or GHRF) is a 44-residue peptide made in the hypothalamus. It acts on the GHRH receptor in the anterior pituitary, which signals the release of growth hormone. Early work on the hormone established that its first 29 residues, with an amidated C-terminus, retain the activity of the full-length peptide. That fragment, GHRH(1-29)NH2, is sermorelin.^[1]

Sermorelin is the only member of this family that has held a regulatory approval. As sermorelin acetate it was sold in the United States under the brand name Geref, first as a diagnostic test of pituitary function and later for idiopathic growth hormone deficiency in children. The manufacturer stopped selling it in 2008, the approvals were withdrawn, and in 2013 the FDA determined that the withdrawal was not for reasons of safety or effectiveness.^[2] Its PubChem record gives the sequence YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH2, the formula C149H246N44O42S and a molecular weight of 3357.9 g/mol for the free peptide amide.^[3] The sermorelin acetate product page lists those identifiers.

The four substitutions in mod GRF 1-29#

Modified GRF (1-29) keeps the length and the amidated end of sermorelin but changes four of its 29 residues. The substitutions can be read directly by comparing sermorelin's sequence with the structure the FDA's Global Substance Registration System records for CJC-1295, whose first 29 residues are the modified peptide.^[3][4]

The resulting 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. Changing two residues to ones a single methylene group heavier (Asn to Gln, Gly to Ala) and replacing the only methionine with leucine gives a formula of C152H252N44O42 and an average molecular weight of about 3,368 g/mol. Those two figures are calculated here from sermorelin's PubChem values and the four changes; we did not find a separate PubChem record for the 29-residue peptide on its own, which is part of the naming problem described below. The 29-residue peptide is what the CJC-1295 (no DAC) product page describes.

What DAC adds: the original CJC-1295#

The molecule first published as CJC-1295 is the modified 29-residue peptide with a lysine added as residue 30 and a maleimidopropionyl group attached to that lysine's side-chain amine. The FDA's substance registry records CJC-1295 under UNII 62RC32V9N7 and CAS number 446262-90-4 with exactly that structure: D-alanine at position 2, a C-terminal lysinamide, and the maleimide-propionyl group on the lysine's N6 nitrogen.^[4] Adding the lysine and the maleimidopropionyl group to the formula above gives C165H269N47O46 and an average molecular weight of about 3,647 g/mol, roughly 280 mass units heavier than the no-DAC peptide.

The maleimide group is the working part. Maleimides react with free thiol groups, and serum albumin carries one free cysteine. The design intent was for the peptide to bond covalently to albumin after administration and so circulate for far longer than a free 29-residue peptide, which plasma enzymes break down quickly.

The published CJC-1295 studies, and what each measured#

Every study below concerns the albumin-binding DAC conjugate. None tested the 29-residue peptide on its own.

Jetté et al., Endocrinology, 2005 (rats)#

This paper describes how the conjugate was chosen. The authors made three maleimido derivatives of human GRF(1-29) and bound them to human serum albumin. All three conjugates resisted degradation by the plasma enzyme dipeptidyl peptidase-IV in vitro and stimulated growth hormone secretion from cultured rat pituitary cells. In rats, the selected compound, CJC-1295, produced about four times the growth hormone area under the curve over two hours compared with GRF(1-29), remained detectable in plasma beyond 72 hours, and was shown by Western blotting to be associated with the albumin band. The work was in cells and rats.^[5]

Teichman et al., Journal of Clinical Endocrinology & Metabolism, 2006 (healthy adults)#

Two randomized, double-blind, placebo-controlled, ascending-dose studies, lasting 28 and 49 days at two sites, enrolled healthy adults aged 21 to 61. The first gave single administrations at four ascending levels; the second gave repeated administrations. The study measured the pharmacokinetics of CJC-1295 and the peak levels and area under the curve of growth hormone and IGF-I. The authors reported dose-dependent increases in mean growth hormone (2- to 10-fold, lasting six days or more after a single administration) and in mean IGF-I (1.5- to 3-fold, lasting 9 to 11 days), IGF-I remaining above baseline for up to 28 days after repeated administration, and an estimated half-life of 5.8 to 8.1 days.^[6]

Ionescu and Frohman, Journal of Clinical Endocrinology & Metabolism, 2006 (healthy men)#

This study asked whether sustained GHRH-receptor stimulation flattens the normal pulsatile pattern of growth hormone secretion. Healthy men aged 20 to 40 had blood sampled every 20 minutes over 12 hours overnight, before and one week after a single administration of CJC-1295 at one of two levels. Pulse frequency and pulse magnitude were unchanged. Trough growth hormone rose 7.5-fold, mean growth hormone rose 46% and IGF-I rose 45%; the two dose levels gave similar responses, and the change in IGF-I did not correlate with any measure of pulsatile secretion. The authors attributed the IGF-I increase mainly to the rise in trough levels.^[7]

What has not been studied: mod GRF 1-29 on its own#

We did not identify a published clinical development program, human pharmacokinetic study or controlled animal study of the tetrasubstituted 29-residue peptide as a product in its own right. Its appearance in the literature is mostly indirect: as the peptide portion of the DAC conjugate, and in forensic work. In 2010 a Norwegian anti-doping laboratory, analysing a preparation seized by police and customs, used liquid chromatography with high-resolution tandem mass spectrometry and found a 29-residue peptide with a C-terminal amide whose sequence matched the peptide marketed as CJC-1295.^[8] In other words, the material circulating under the CJC-1295 name was already the no-DAC peptide, not the conjugate the clinical papers describe.

• The 6 to 8 day half-life reported in humans depends on albumin binding and does not apply to a peptide that lacks the maleimide linker.
• The growth hormone and IGF-I findings in healthy adults were obtained with the DAC conjugate only.
• No published human safety, pharmacokinetic or efficacy data exist for the no-DAC peptide.
• Neither molecule is approved by any regulator.

Regulatory status of CJC-1295#

No CJC-1295 product, with or without DAC, has been approved by the FDA. The FDA's list of bulk drug substances that may present significant safety risks in compounding includes CJC-1295 in its table of nominations that were later withdrawn. In that entry the agency cites serious adverse events associated with CJC-1295, including increased heart rate and a systemic vasodilatory reaction, states that available clinical data are limited, and notes a possible risk of immunogenicity for certain routes. The entry does not say which form was nominated.^[9]

In sport, the World Anti-Doping Agency's 2026 Prohibited List names CJC-1295, with sermorelin and tesamorelin, as examples of GHRH and its analogues in section S2.2.4, a class prohibited at all times, in and out of competition.^[10]

What a CJC-1295 no DAC Certificate of Analysis should show#

Because the two molecules differ by about 280 mass units, mass spectrometry separates them unambiguously, and a report for a no-DAC lot should show a measured mass consistent with the 29-residue peptide (about 3,368 g/mol average mass, or the corresponding charge states on an electrospray spectrum), not one near 3,647. Beyond that, the elements are the same as for any peptide: the lot number on the vial, the HPLC method and purity figure with its chromatogram, the identity method, the issuing laboratory and the date. Our guides to reading a Certificate of Analysis and to HPLC and mass spectrometry explain each item, and the COA library lists every Renuvia lot and its current testing status. The CJC-1295 + Ipamorelin product page describes a two-peptide vial that contains the same no-DAC peptide.