CJC-1295 with and without DAC: one name, two molecules
The name CJC-1295 is attached in the literature to two different molecules, one carrying a drug affinity complex (DAC) and one without it.[1],[2],[3]
The DAC form ends in a reactive group meant to attach the peptide to serum albumin, an approach its developers describe as a way to extend plasma half-life, and the form without DAC has no such group.[4],[5]
Each column below is sourced only to work on that exact molecule, so no measurement made on one form is attributed to the other.[1],[2]
Identity side by side
| Attribute | CJC-1295 (with DAC) | CJC-1295 (no DAC) |
|---|---|---|
| Also recorded as[1],[2] | CJC-1295 with DAC; DAC:GRF | Modified GRF (1-29); CJC-1295 without DAC; Mod GRF 1-29 |
| Library classification[1],[2] | Growth-hormone-releasing hormone analogue | Growth-hormone-releasing hormone analogue without drug affinity complex |
| Structure as published[4],[5] | Tetrasubstituted hGRF(1-29) plus a C-terminal lysine bearing an Nε-3-maleimidopropionamide group | (D-Ala2, Gln8, Ala15, Leu27)-GRF amide, 29 residues |
| Substituted positions named by the cited source[4],[5] | Four substitutions stated; positions not named in the abstract | Positions 2, 8, 15 and 27 |
| C-terminal addition[4],[5] | Lysine carrying a 3-maleimidopropionamide group | None: no lysine extension and no maleimide |
| Albumin attachment[4],[5] | Designed to react with the free thiol of albumin cysteine 34; immunoreactivity found on the albumin band in rat plasma | No albumin-reactive group recorded |
| Half-life reported[6],[7],[5] | 5.8 to 8.1 days (Teichman 2006); 8 days (Ionescu 2006) | None published; detected intact in rat plasma up to the last sample at 8 hours, qualitatively |
| Molecular formula (library)[1] | C165H269N47O46 | Not recorded in this library |
| Receptor recorded (library)[1],[3] | Growth-hormone-releasing hormone receptor | None; no study measuring a response was found |
| Kind of published record[4],[6],[3],[5],[8] | Discovery chemistry, rat plasma work and human pharmacokinetic studies | Analytical chemistry: urine and rat plasma detection, seized-powder identification |
What does the drug affinity complex add to the peptide?
The 2005 discovery paper describes CJC-1295 as human GRF(1-29) with four substitutions, extended at its C-terminal end by a lysine that carries a 3-maleimidopropionamide group.[4]
That maleimide was positioned to bond with the free thiol on cysteine 34 of serum albumin, and it was chosen as the most active of three maleimido derivatives the authors made.[4]
Western blots of rat plasma placed a CJC-1295-reactive signal on the serum albumin band from 15 minutes onward, still detectable past 24 hours.[4]
Two later human studies of this conjugated form report half-life estimates of 5.8 to 8.1 days and of 8 days, and the second describes the analogue as binding permanently to endogenous albumin.[6],[7]
What is recorded for the form without DAC?
A 2016 plasma detection study prints the analyte it calls CJC-1295 by sequence: 29 amidated residues with substitutions at positions 2, 8, 15 and 27, no lysine extension and no maleimide.[5]
A 2021 urine study listed CJC-1295 and CJC-1295 with drug affinity complex as two separate analytes, the only publication cited here that names both molecules.[3]
None of the publications found for the unconjugated form reports a receptor measurement, a hormone response or a pharmacokinetic parameter.[3],[5]
How is each form described as resisting breakdown?
For the DAC form, albumin conjugates of all three maleimido derivatives showed increased stability against dipeptidyl peptidase IV in vitro, and CJC-1295 was found in rat plasma beyond 72 hours.[4]
For the form without DAC, the 2016 authors linked the absence of N-terminally shortened metabolites in rats to the D-alanine at position 2.[5]
That rat work reported qualitative detection only and made no pharmacokinetic interpretation, so its 8-hour sampling window is not a half-life.[5]
What does this comparison not establish?
The discovery abstract for the DAC form does not name its four substituted residues, so this page does not assert that they are the same four printed for the unconjugated form.[4],[5]
No study cited here measured both forms in one living system, and the hormone and half-life data for the DAC form are not carried across to the other column.[6],[3]
Limitations
Powders seized in Denmark and sold as modified GRF (1-29) carried an extra N-terminal glycine, so a product name alone does not settle which molecule a sample contains.[8]
The structures above are the ones the cited publications describe; none of them is an analysis of any lot supplied by PepGenex.[4],[5]
Compound profiles
References
- CJC-1295 research profile, PepGenex Science (identity and records, with their sources).
- CJC-1295 (no DAC) research profile, PepGenex Science (identity and records, with their sources).
- Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V.. Advances in the detection of growth hormone releasing hormone synthetic analogs.. Drug Testing and Analysis 2021. PMID 34665524 · DOI 10.1002/dta.3183
- Jetté L, Léger R, Thibaudeau K, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058. PMID 15817669 · DOI 10.1210/en.2004-1286
- Knoop A, Thomas A, Fichant E, Delahaut P, Schänzer W, Thevis M.. Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS.. Analytical and Bioanalytical Chemistry 2016. PMID 26879649 · DOI 10.1007/s00216-016-9377-3 · PMC4830873
- Teichman SL, Neale A, Lawrence B, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683 · DOI 10.1210/jc.2005-1536
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PMID 17018654 · DOI 10.1210/jc.2006-1702
- Gajda PM, Holm NB, Hoej LJ, Rasmussen BS, Dalsgaard PW, Reitzel LA, Linnet K.. Glycine-modified growth hormone secretagogues identified in seized doping material.. Drug Testing and Analysis 2019. PMID 30136411 · DOI 10.1002/dta.2489