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Educational Reference · Research-Use-Only

CJC-1295 (DAC): Mechanism, Research, and Regulatory Status

A research-grade overview of CJC-1295 (DAC) — what it is, how it works at the molecular level, what published studies have shown, and answers to the questions researchers ask most.

5 peer-reviewed references5 linked to PubMed / DOI2 published human trials

Last reviewed 2026-07-28

Sequence
Modified human GHRH(1-29) scaffold with D-Ala2, Gln8, Ala15 and Leu27 substitutions, plus a C-terminal N-epsilon-3-maleimidopropionamide lysine (the DAC moiety)
Mol. Weight
3647.25 g/mol
Form
Lyophilized powder
CAS

What is CJC-1295 (DAC)?

CJC-1295 is a synthetic analog of growth hormone-releasing hormone based on the biologically active N-terminal 1-29 fragment of human GHRH. It acts as an agonist at the GHRH receptor, a class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs, where receptor occupancy elevates intracellular cAMP and promotes synthesis and pulsatile release of endogenous growth hormone, which in turn drives hepatic IGF-1 production. Four amino acid substitutions relative to native GHRH(1-29) confer resistance to enzymatic inactivation, most importantly the D-alanine at position 2, which blocks cleavage by dipeptidyl peptidase-IV, the principal route of GHRH degradation in plasma.

The DAC variant additionally carries a maleimidopropionyl group on a C-terminal lysine, which reacts selectively with the free thiol of Cys34 on circulating serum albumin to form a covalent bioconjugate in vivo. Jette and colleagues established this albumin-tethering strategy as the basis for the compound's extended plasma residence, with an estimated half-life of 5.8 to 8.1 days reported in healthy adults by Teichman and colleagues. Because the mechanism acts upstream at the pituitary rather than supplying exogenous growth hormone, output remains subject to negative feedback from somatostatin and IGF-1; Ionescu and Frohman reported that the frequency and magnitude of GH secretory pulses were unaltered despite continuous receptor stimulation, with basal GH rather than pulse amplitude accounting for the increase.

CJC-1295 without DAC, commonly marketed as modified GRF 1-29, lacks the maleimide moiety and therefore does not form the albumin conjugate, giving it a fundamentally different pharmacokinetic profile.

Research highlights

What published peer-reviewed research and preclinical studies have established about CJC-1295 (DAC):

  • 01Jette and colleagues identified CJC-1295 as a hGRF(1-29) analog that conjugates in vivo to the free thiol on Cys34 of serum albumin, with plasma detectability beyond 72 hours and a 4-fold increase in GH AUC over 2 hours versus hGRF(1-29).
  • 02In healthy adults, single doses produced dose-dependent 2- to 10-fold increases in mean plasma GH for 6 days or more and 1.5- to 3-fold increases in IGF-1 for 9 to 11 days; estimated half-life was 5.8 to 8.1 days (Teichman 2006).
  • 03GH pulsatility was preserved under continuous stimulation: pulse frequency and magnitude were unaltered while basal GH rose 7.5-fold, giving a 46% increase in mean GH and 45% increase in IGF-1 (Ionescu 2006).
  • 04Once-daily administration normalized growth in the GHRH knockout mouse (Alba 2006).
  • 05Activation of the GH/IGF-1 axis by CJC-1295 produced measurable serum protein profile changes in normal adult subjects (Sackmann-Sala 2009).
  • 06Clinical development did not progress beyond early-phase studies and was discontinued; no efficacy trials for any indication were completed.

Published clinical and preclinical research

Ascending-dose safety, tolerability and PK/PD of CJC-1295 in healthy adults

Phase 1 · 2006

Dose-dependent 2- to 10-fold increases in mean plasma GH for at least 6 days and 1.5- to 3-fold increases in IGF-1 for 9 to 11 days after a single injection; IGF-1 remained elevated up to 28 days after multiple doses. Estimated half-life 5.8 to 8.1 days. No serious adverse reactions reported.

N ·
Duration · 28 days (trial 1) and 49 days (trial 2)
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683.

GH secretory pulsatility during continuous stimulation by CJC-1295

Phase 1 · 2006

Pulsatility preserved — pulse frequency and magnitude unaltered. Basal GH increased 7.5-fold, mean GH increased 46%, IGF-1 increased 45%.

N ·
Duration · Single injection; 12-hour overnight sampling at 20-minute intervals
Ionescu M, Frohman LA. J Clin Endocrinol Metab. 2006;91(12):4792-7. PMID 17018654.

Frequently asked questions about CJC-1295 (DAC)

What is the difference between CJC-1295 with and without DAC?+

This is the most common point of confusion. The DAC (Drug Affinity Complex) version carries a maleimidopropionyl group on a C-terminal lysine that reacts covalently with Cys34 of serum albumin, tethering the peptide to albumin and extending plasma residence to an estimated 5.8 to 8.1 days. CJC-1295 without DAC — often sold as modified GRF 1-29 — lacks that moiety, forms no albumin conjugate, and has a fundamentally shorter pharmacokinetic profile. They are not interchangeable in experimental design.

How does it differ from GHRP-class secretagogues?+

CJC-1295 is a GHRH analog acting at the GHRH receptor on pituitary somatotrophs. GHRP-class compounds such as ipamorelin and GHRP-6 act at a distinct receptor, the growth hormone secretagogue receptor (ghrelin receptor). Because the two classes engage different receptors, they are studied both separately and in combination in the published literature.

Why does DPP-IV resistance matter?+

Dipeptidyl peptidase-IV is the principal route of native GHRH degradation in plasma, cleaving the peptide near its N-terminus. The D-alanine substitution at position 2 blocks that cleavage, which is what allows the analog to persist long enough for the albumin-conjugation strategy to be useful.

Does continuous stimulation abolish GH pulsatility?+

Published work indicates it does not. Ionescu and Frohman reported that pulse frequency and magnitude were unaltered under continuous receptor stimulation, with the increase in mean GH attributable to a 7.5-fold rise in basal GH rather than to changes in pulse architecture. This is consistent with the mechanism acting upstream, leaving somatostatin and IGF-1 feedback intact.

How should it be stored and handled?+

Store lyophilized material at -20C, desiccated and protected from light. The maleimide group that defines the DAC variant is thiol-reactive and moisture-sensitive, so avoid reducing agents and thiol-containing buffers that would consume it before albumin conjugation, and keep the powder rigorously dry. Aliquot reconstituted stocks and avoid repeated freeze-thaw.

References & sources

Every citation below was resolved against its primary source before publication — each PMID against the PubMed record and each DOI through doi.org. Follow any link to read the paper at the publisher rather than taking our summary on trust.

  1. [1]Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. Journal of Clinical Endocrinology and Metabolism. 2006. PMID: 16352683 DOI: 10.1210/jc.2005-1536
  2. [2]Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology and Metabolism. 2006. PMID: 17018654 DOI: 10.1210/jc.2006-1702
  3. [3]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. Endocrinology. 2005. PMID: 15817669 DOI: 10.1210/en.2004-1286
  4. [4]Alba M, Fintini D, Sagazio A, et al.. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American Journal of Physiology - Endocrinology and Metabolism. 2006. PMID: 16822960 DOI: 10.1152/ajpendo.00201.2006
  5. [5]Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Hormone and IGF Research. 2009. PMID: 19386527 DOI: 10.1016/j.ghir.2009.03.001

Where this data comes from

  • Citations & trial data: PubMed (NCBI, U.S. National Library of Medicine), Crossref and ClinicalTrials.gov.
  • Chemical identity: PubChem and UniProt. Where sources conflicted, the disputed value is omitted rather than guessed.
  • Regulatory status: U.S. FDA publications and, where applicable, the WADA Prohibited List. Compounding status changes frequently — verify against FDA directly before relying on it.
  • Purity, form and storage are handling and supplier conventions, not literature-derived values. Confirm against the lot-specific certificate of analysis.

Content last reviewed 2026-07-28. Compiled by Veridian Research from the primary literature. This page is an educational reference for laboratory researchers — it is not medical advice, and it describes no human use.

Regulatory status

CJC-1295 is not approved by the FDA or any comparable regulatory authority for any indication in any jurisdiction. Clinical development did not proceed beyond early-phase studies and was discontinued, leaving it categorized as an abandoned drug candidate with no completed efficacy trials. GHRH analogs, expressly including CJC-1295, fall under WADA Prohibited List section S2 and are prohibited at all times both in and out of competition; validated detection methods exist for human and equine testing. Compounding status under the FDA 503A bulk drug substances framework has been subject to ongoing review and change; verify against FDA's currently published list rather than any secondary source. Supplied strictly as a research chemical for in vitro and laboratory research use only.

Research-Use-Only Material

Specifications and certificate of analysis

CJC-1295 (DAC) is stocked as a research reagent. Analytical documentation — identity, purity and the lot-specific certificate of analysis — is published on the product record.

View specifications & COA →

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