CJC-1295 (No DAC) 5 mg

CJC-1295 (No DAC) is a synthetic 29-residue peptide built on the first 29 amino acids of human growth-hormone-releasing hormone, the hypothalamic peptide written in the older literature as GRF and in newer work as GHRH. The native human hormone is principally a 44-residue C-terminal amide, and the 1-29 amide fragment is the scaffold this molecule is built on. Four residues differ from that fragment. Position 2 carries D-alanine in place of L-alanine, position 8 carries glutamine in place of asparagine, position 15 carries alanine in place of glycine, and position 27 carries leucine in place of methionine. Those four changes are why the primary literature calls the molecule modified GRF(1-29), or tetrasubstituted GRF(1-29). Cayman Chemical files three names against its reference material for the same structure: CJC-1295-no DAC, Modified GRF (1-29), and GHRH (1-29)-NH2. The full sequence is YADAIFTQSYRKVLAQLSARKLLQDILSR, with D-alanine at position 2 and a C-terminal amide rather than a free acid. The amide is not a cosmetic detail: it is what separates the published formula C152H252N44O42 from the free-acid form of the same sequence, which would be C152H251N43O43.

The name CJC-1295 originally belongs to a longer molecule. Jette and colleagues (2005) defined CJC-1295 as a tetrasubstituted form of hGRF(1-29) carrying an extra lysine at the C-terminus whose side-chain amine bears an N-epsilon-3-maleimidopropionamide group. That maleimide is the Drug Affinity Complex, or DAC: a thiol-reactive handle that forms a covalent bond to the free cysteine-34 thiol of serum albumin after injection. Strip the Lys30-maleimide extension away and thirty residues become twenty-nine. What remains is the peptide supplied here. 'CJC-1295 without DAC' is therefore a market name for the tetrasubstituted GRF(1-29) backbone, and not the compound characterised under the CJC-1295 name in the original pharmacology papers. The two are distinguishable by mass: 3367.9 g/mol for the 29-residue amide against 3647.3 g/mol for the 30-residue maleimide conjugate, whose formula is C165H269N47O46. The difference is about 279 mass units.

Molecular formula C152H252N44O42, average molecular weight 3367.9 g/mol, computed for PubChem CID 91976842 and listed independently by Cayman Chemical and ChemicalBook. We are leaving the CAS field on this page blank rather than guessing, and the reason is worth stating plainly. Public registries do not agree on which number belongs to the no-DAC form. Cayman Chemical, GLPBio and Biosynth use 446036-97-1. A large share of peptide vendors use 863288-34-0. ChemicalBook publishes both numbers, on two separate pages that carry the identical molecular formula, the identical molecular weight and the identical 29-residue sequence, which is a direct contradiction inside a single source. ChemBlink files 863288-34-0 with the 29-residue sequence alongside a formula and mass that match neither the no-DAC peptide nor the DAC conjugate. A third number, 446262-90-4, is used for the DAC conjugate. CAS Common Chemistry, the registry that would settle the question, is not publicly queryable without a key. A blank field is more useful to a researcher than a confident wrong one, and the formula, mass and sequence above identify the compound unambiguously without it.

The peer-reviewed record for this exact 29-residue molecule is thin, and it is worth stating that plainly. Almost every published pharmacology and clinical study carrying the CJC-1295 name used the 30-residue albumin-binding conjugate, not the unconjugated backbone sold here. What does exist for the backbone itself is the structure-activity chemistry that explains why each of the four substitutions is present, together with analytical work from anti-doping laboratories. No peer-reviewed human trial of the unconjugated peptide was identified during preparation of this page.

Each substitution traces to a specific published finding. Frohman and colleagues (1989) characterised the plasma enzyme responsible for the primary proteolytic cleavage of GHRH at the 2-3 amino acid bond and identified it as dipeptidylpeptidase IV; conversion to GRH(3-44)-NH2 was blocked by diprotin A, a competitive DPP-IV inhibitor, and D-amino-acid substitution at either position 1 or position 2 also prevented hydrolysis. The same study reported that native GRH exhibited trypsin-like degradation at the 11-12 position, while cleavage at the 12-13 site occurred only with the shortened GRH(1-32)-NH2 and GRH(1-29)-NH2 forms, and concluded that degradation in plasma occurs primarily by DPP-IV and to a lesser extent by trypsin-like enzymes.

Campbell and colleagues (1994) set out the two chemical liabilities of the native hormone: hGRF(1-44)-NH2 is subject to rearrangement of Asn8 to Asp8 and beta-Asp8 by way of aminosuccinimide formation, and to oxidation of Met27 to the sulfoxide in aqueous environments, both of which they report as greatly reducing bioactivity. Substituting Gln8, which they annotate as not naturally occurring, for Asn8 gave analogues with enhanced aqueous stability in vitro, which they gloss as a decreased rate of isomerisation. One caveat belongs with that result: the analogues they built and bioassayed were [His1,Val2,Thr/Gln8,Ala15,Leu27]hGRF(1-32)-OH compounds, not the 29-residue amide supplied here, so the finding explains why Gln8 is present rather than describing this molecule directly.

The Ala15 change was quantified separately. Campbell and colleagues (1991) reported that hGRF(1-29)-NH2 analogues carrying alanine in place of glycine at position 15 displayed 4 to 5 times higher affinity for the GRF receptor than hGRF(1-44)-NH2, and that GH-releasing activity in vitro was directly correlated with GRF receptor binding affinity for all hGRF analogues they examined. Replacing Gly15 with sarcosine instead produced what the authors describe as a dramatic loss of activity and receptor binding. The same paper found that fragments of hGRF representative of DPP-IV and trypsin-like cleavage are inactive as a consequence of greatly diminished GRF receptor binding. The authors attributed the Ala15 effect to increased amphiphilic alpha-helical interactions.

Jette and colleagues (2005) synthesised three maleimido derivatives of hGRF(1-29) and bioconjugated them to human serum albumin ex vivo. All three conjugates showed enhanced in-vitro stability against dipeptidylpeptidase-IV and were bioactive in a GH secretion assay in cultured rat anterior pituitary cells. Administered subcutaneously to normal male Sprague-Dawley rats, the best of the three, designated CJC-1295, showed a 4-fold increase in GH area under the curve over a 2-hour period compared with hGRF(1-29), and was found to be present in plasma beyond 72 hours. Western blot of plasma from an injected rat showed a CJC-1295 immunoreactive species on the band corresponding to serum albumin, appearing after 15 minutes and remaining in circulation beyond 24 hours. The comparator in that experiment was hGRF(1-29); the paper does not report a separate arm for the unconjugated tetrasubstituted backbone.

Two human studies published in 2006 used the conjugate, and their numbers should not be read across to this product. Teichman and colleagues ran two randomised, placebo-controlled, double-blind ascending-dose trials of 28 and 49 days in healthy subjects aged 21 to 61. After subcutaneous administration of a single dose they reported dose-dependent increases in mean plasma GH concentrations of 2- to 10-fold for 6 days or more, and in mean plasma IGF-I concentrations of 1.5- to 3-fold for 9 to 11 days, with an estimated CJC-1295 half-life of 5.8 to 8.1 days. Ionescu and Frohman used 20-minute blood sampling across an overnight 12-hour period in healthy men aged 20 to 40, before and one week after a single 60 or 90 microgram per kilogram injection. They reported that the frequency and magnitude of GH secretory pulses were unaltered, while basal trough GH levels were markedly increased 7.5-fold (P less than 0.0001), mean GH levels rose 46 percent (P less than 0.01) and IGF-I levels rose 45 percent (P less than 0.001), with no significant difference between the two doses. Both papers describe a molecule with an albumin-bound half-life of roughly 8 days. The unconjugated peptide has no such handle.

Analytical chemists have also examined what is actually inside preparations sold under this name. Henninge and colleagues (2010), working on unknown pharmaceutical preparations submitted by Norwegian police and customs authorities, used liquid chromatography with high-resolution tandem mass spectrometry and found a 29-amino-acid peptide with a C-terminal amide function, from which an amino acid sequence was proposed. That result matters for identity testing rather than pharmacology: the 29-residue amide and the 30-residue maleimide conjugate differ by roughly 279 mass units and are straightforward to tell apart, yet material has been sold under one name while being the other. The authors note that CJC-1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List.