CJC with or without DAC?

CJC-1295 (GHRH Analog): Mechanism & Comparison of DAC vs. No-DAC in Animal Studies

This article summarizes peer-reviewed findings on CJC-1295, a long-acting analog of growth-hormone-releasing hormone (GHRH). We focus on mechanism and animal-model evidence comparing DAC (Drug Affinity Complex) variants versus short-acting GHRH(1-29) analogs (often colloquially called “no-DAC”). No dosages or usage regimens are discussed, and no uses outside physician-directed care are suggested.

CJC-1295 at a glance

Class Long-acting GHRH analog designed to enhance endogenous GH release via the pituitary GHRH receptor.
Intent Prolong GH–IGF-1 axis activation vs. native GHRH(1-29), which is rapidly cleared. [oai_citation:0‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC423714/?utm_source=chatgpt.com) [oai_citation:1‡PubMed](https://pubmed.ncbi.nlm.nih.gov/2866222/?utm_source=chatgpt.com)
DAC “DAC” denotes a chemical strategy enabling in vivo binding to serum albumin to extend peptide residence time. [oai_citation:2‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com) [oai_citation:3‡PubMed](https://pubmed.ncbi.nlm.nih.gov/23639804/?utm_source=chatgpt.com)

Mechanism of Action & Half-Life Extension

GHRH receptor agonism

CJC-1295 is based on a tetrasubstituted GHRH(1-29) core that activates the pituitary GHRH receptor, increasing pulsatile GH secretion and secondarily IGF-1 production—core features of the GH–IGF-1 axis. [oai_citation:4‡Oxford Academic](https://academic.oup.com/jcem/article/91/3/799/2843281?utm_source=chatgpt.com) [oai_citation:5‡PubMed](https://pubmed.ncbi.nlm.nih.gov/16352683/?utm_source=chatgpt.com)

What “DAC” changes

DAC technology introduces a reactive handle that allows covalent association with endogenous serum albumin after administration. This albumin coupling slows clearance and markedly prolongs exposure compared with short-acting GHRH(1-29) analogs. [oai_citation:6‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com) [oai_citation:7‡Oxford Academic](https://academic.oup.com/jcem/article-pdf/91/3/799/10779632/jcem0799.pdf?utm_source=chatgpt.com)

Why short-acting analogs are brief

Native GHRH(1-29) and early analogs exhibit rapid enzymatic degradation and short plasma half-lives (minutes) in both animals and humans, leading to transient GH peaks. [oai_citation:8‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC423714/?utm_source=chatgpt.com) [oai_citation:9‡PubMed](https://pubmed.ncbi.nlm.nih.gov/2866222/?utm_source=chatgpt.com)

Animal Data: DAC vs. Short-Acting GHRH(1-29) Analogs

Rats: albumin-binding analogs (including CJC-1295) vs. hGRF(1-29)

In male Sprague–Dawley rats, investigators screened albumin-binding bioconjugates of GHRH(1-29). The candidate that became CJC-1295 produced a substantially greater GH area-under-the-curve over 2 hours than native hGRF(1-29), consistent with enhanced exposure and receptor engagement due to albumin association. [oai_citation:10‡PubMed](https://pubmed.ncbi.nlm.nih.gov/15817669/?utm_source=chatgpt.com)

Short-acting GHRH(1-29) analogs

By contrast, native or minimally modified GHRH(1-29) shows short elimination half-lives after IV dosing in rats (on the order of ~10 minutes in classic pharmacokinetic work), aligning with brief GH elevations unless repeatedly administered. [oai_citation:11‡PubMed](https://pubmed.ncbi.nlm.nih.gov/2866222/?utm_source=chatgpt.com)

Mechanistic interpretation

The key differentiator in animal models is exposure time: DAC-enabled analogs (CJC-1295) leverage albumin to extend the window of GHRH receptor stimulation, whereas short-acting GHRH(1-29) analogs produce transient receptor activation. This pharmacokinetic separation explains the larger GH AUC seen with the DAC construct under matched experimental windows. [oai_citation:12‡PubMed](https://pubmed.ncbi.nlm.nih.gov/15817669/?utm_source=chatgpt.com) [oai_citation:13‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com)

Human Context (Mechanistic Alignment, Not Treatment Advice)

Although this article centers on animal data, clinical pharmacology papers help illustrate the same mechanism: in healthy adults, long-acting CJC-1295 increased mean (and trough) GH and sustained IGF-1, while preserving pulsatility—consistent with extended but physiologic stimulation of the pituitary. These observations echo the albumin-binding rationale demonstrated in animals. [oai_citation:14‡PubMed](https://pubmed.ncbi.nlm.nih.gov/16352683/?utm_source=chatgpt.com)

Limitations & Species Considerations

Species differences in albumin (including polymorphisms and binding behavior) can influence the magnitude of any albumin-mediated half-life extension; results in one species may not translate quantitatively to another. [oai_citation:15‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3231859/?utm_source=chatgpt.com) [oai_citation:16‡PubMed](https://pubmed.ncbi.nlm.nih.gov/23639804/?utm_source=chatgpt.com)

Additionally, terminology like “no-DAC CJC-1295” is used informally in some communities to describe short-acting GHRH(1-29) analogs (e.g., “modified GRF(1-29)”). In primary literature, these are usually referenced generically as GHRH(1-29) analogs rather than “CJC-1295 without DAC.” [oai_citation:17‡PubMed](https://pubmed.ncbi.nlm.nih.gov/9513600/?utm_source=chatgpt.com)

Selected References (PubMed/PMC)

Teichman SL et al. Prolonged stimulation of GH and IGF-1 by CJC-1295 in healthy adults (JCEM, 2006). PubMed/Full text. [oai_citation:18‡PubMed](https://pubmed.ncbi.nlm.nih.gov/16352683/?utm_source=chatgpt.com) [oai_citation:19‡Oxford Academic](https://academic.oup.com/jcem/article/91/3/799/2843281?utm_source=chatgpt.com)
Jetté L et al. hGRF(1-29)–albumin bioconjugates in rats; identification of CJC-1295 (Endocrinology, 2005). [oai_citation:20‡PubMed](https://pubmed.ncbi.nlm.nih.gov/15817669/?utm_source=chatgpt.com)
Sackmann-Sala L et al. Activation of the GH/IGF-1 axis by long-acting GHRH analogs (review) (2009). [oai_citation:21‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com) [oai_citation:22‡PubMed](https://pubmed.ncbi.nlm.nih.gov/19386527/?utm_source=chatgpt.com)
Ionescu M et al. Pulsatile GH secretion persists during CJC-1295 (2006). [oai_citation:23‡PubMed](https://pubmed.ncbi.nlm.nih.gov/17018654/?utm_source=chatgpt.com)
Frohman LA et al. Rapid enzymatic degradation of GHRH (mechanistic basis for short half-life) (1986). [oai_citation:24‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC423714/?utm_source=chatgpt.com)
Rafferty B et al. GHRH(1-29) pharmacokinetics in rats: brief half-lives (1985/1988). [oai_citation:25‡PubMed](https://pubmed.ncbi.nlm.nih.gov/2866222/?utm_source=chatgpt.com)
Sleep D et al. Albumin as a platform for drug half-life extension (review) (2013). [oai_citation:26‡PubMed](https://pubmed.ncbi.nlm.nih.gov/23639804/?utm_source=chatgpt.com)
Schally AV et al. Development of GHRH agonists/antagonists (review) (2024). [oai_citation:27‡PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC12137413/?utm_source=chatgpt.com)

Disclaimer: This page is for scientific and educational purposes only. It summarizes mechanisms and published studies and does not provide medical advice, dosing, or usage guidance. Any consideration of GHRH analogs belongs strictly under physician care within applicable regulations.