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 โ€œno-DACโ€). 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 GHโ€“IGF-1 axis activation vs. native GHRH(1-29), which is rapidly cleared. [oai_citation:0โ€กPMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC423714/?utm_source=chatgpt.com) [oai_citation:1โ€กPubMed](https://pubmed.ncbi.nlm.nih.gov/2866222/?utm_source=chatgpt.com)
  • DAC โ€œDACโ€ denotes a chemical strategy enabling in vivo binding to serum albumin to extend peptide residence time. [oai_citation:2โ€กPMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com) [oai_citation:3โ€กPubMed](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 productionโ€”core features of the GHโ€“IGF-1 axis. [oai_citation:4โ€กOxford Academic](https://academic.oup.com/jcem/article/91/3/799/2843281?utm_source=chatgpt.com) [oai_citation:5โ€กPubMed](https://pubmed.ncbi.nlm.nih.gov/16352683/?utm_source=chatgpt.com)

What โ€œDACโ€ 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:6โ€กPMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2787983/?utm_source=chatgpt.com) [oai_citation:7โ€กOxford 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:8โ€กPMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC423714/?utm_source=chatgpt.com) [oai_citation:9โ€กPubMed](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 Spragueโ€“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:10โ€กPubMed](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:11โ€กPubMed](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:12โ€กPubMed](https://pubmed.ncbi.nlm.nih.gov/15817669/?utm_source=chatgpt.com) [oai_citation:13โ€กPMC](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 pulsatilityโ€”consistent with extended but physiologic stimulation of the pituitary. These observations echo the albumin-binding rationale demonstrated in animals. [oai_citation:14โ€กPubMed](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:15โ€กPMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3231859/?utm_source=chatgpt.com) [oai_citation:16โ€กPubMed](https://pubmed.ncbi.nlm.nih.gov/23639804/?utm_source=chatgpt.com)

Additionally, terminology like โ€œno-DAC CJC-1295โ€ is used informally in some communities to describe short-acting GHRH(1-29) analogs (e.g., โ€œmodified GRF(1-29)โ€). In primary literature, these are usually referenced generically as GHRH(1-29) analogs rather than โ€œCJC-1295 without DAC.โ€ [oai_citation:17โ€กPubMed](https://pubmed.ncbi.nlm.nih.gov/9513600/?utm_source=chatgpt.com)

Selected References (PubMed/PMC)

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