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MOD-GRF-1-29

Mod GRF 1-29 (CJC-1295 without DAC): A Stabilised GHRH(1-29) Analogue

Research summary. Modified GRF (Mod GRF) 1-29, also known as CJC-1295 without DAC, is a 29-residue truncated and amino-acid-substituted analogue of growth-hormone-releasing hormone (GHRH). It is a research-grade GHRH agonist used in growth-hormone-axis studies as a short-acting counterpart to CJC-1295 with DAC (the long-acting albumin-binding analogue covered in a separate post). Mod GRF 1-29 retains the four engineered amino-acid substitutions that protect against dipeptidyl peptidase-4 (DPP-4) cleavage and other proteolytic degradation pathways, but lacks the maleimide DAC linker that confers extended in vivo half-life on CJC-1295 with DAC.

Molecular profile

  • Sequence: Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH₂ (29 residues, C-terminal amide)
  • Molecular formula: C₁₅₂H₂₅₂N₄₄O₄₂
  • Molecular weight: ~3368.7 g/mol
  • Class: GHRH receptor agonist (truncated and stabilised GHRH(1-29) analogue)
  • Synonyms: Mod GRF 1-29, CJC-1295 No DAC, CJC-1295 without DAC
  • Distinction: Same core sequence as CJC-1295 (with DAC), without the maleimide-containing DAC moiety that drives albumin binding and ~5–8-day plasma half-life

Engineered substitutions

The four amino-acid substitutions distinguishing Mod GRF 1-29 from native GHRH(1-29) are conventionally identified as:

  • D-Ala at position 2: protects against DPP-4 cleavage between positions 2 and 3, the dominant proteolytic degradation route of native GHRH.
  • Gln at position 8: reduces susceptibility to oxidative deamidation.
  • Ala at position 15: improves bioactivity and stability.
  • Leu at position 27: protects against trypsin-like cleavage near the C-terminus.

These substitutions produce a substantially more stable molecule than native GHRH(1-29), but in the absence of the DAC linker the in vivo half-life remains short (on the order of ~30 minutes), giving Mod GRF 1-29 a pharmacokinetic profile much more similar to sermorelin than to CJC-1295 with DAC.

Mechanism of action

Mod GRF 1-29 is an agonist at the GHRH receptor (GHRH-R) on anterior pituitary somatotrophs. Receptor binding activates Gαs, elevates intracellular cAMP, and drives pulsatile growth hormone (GH) release into systemic circulation. Downstream, hepatic IGF-1 production rises in proportion to integrated GH exposure.

Because Mod GRF 1-29 acts on the GHRH-R and is short-acting, it preserves the normal pulsatile pattern of GH secretion — a property that is often contrasted in research contexts with the more sustained GH elevation produced by CJC-1295 with DAC.

Position relative to related GHRH analogues

  • Sermorelin: GHRH(1-29) without engineered substitutions; very short half-life; the original short-acting GHRH analogue and at one point an FDA-approved diagnostic agent for GH deficiency (since withdrawn from the U.S. market for commercial reasons rather than safety concerns).
  • Mod GRF 1-29 (CJC-1295 No DAC): GHRH(1-29) with the four engineered substitutions, no DAC; short-acting research peptide with improved metabolic stability over sermorelin but still pulsatile.
  • CJC-1295 with DAC: Same core sequence as Mod GRF 1-29 with the addition of a maleimide DAC linker that binds covalently to plasma albumin, producing a ~5–8-day half-life and sustained GH-axis stimulation.
  • Tesamorelin: Trans-3-hexenoyl-modified GHRH(1-44); FDA-approved for HIV-associated lipodystrophy.

Preclinical research applications

Research interest in Mod GRF 1-29 is concentrated in:

  • Studies of pulsatile versus sustained GHRH-receptor activation in GH-axis biology.
  • Co-administration studies with ghrelin-receptor agonists (GHRP-2, GHRP-6, ipamorelin, hexarelin), where the synergy between GHRH-R and GHSR-1a activation produces additive pulsatile GH release that exceeds either compound alone.
  • Comparator-control work alongside sermorelin and CJC-1295 with DAC to dissect the contributions of metabolic stability versus albumin binding to overall GH-axis pharmacology.

Current research status

Mod GRF 1-29 is an investigational research peptide. It is not approved by the FDA for any indication. The closely related sermorelin (the unsubstituted parent sequence) was historically FDA-approved for diagnostic use in GH deficiency but has been withdrawn from the U.S. market. Tesamorelin remains the only currently FDA-approved GHRH-class agent in the United States.

For research-supplier contexts, Mod GRF 1-29 is supplied as a research-grade investigational peptide and is not intended for self-administration.

Key takeaways for researchers

  • Mod GRF 1-29 (CJC-1295 No DAC) is a stabilised 29-residue GHRH analogue with four engineered amino-acid substitutions that protect against DPP-4 and other proteolytic cleavage.
  • It is short-acting (half-life on the order of ~30 minutes), producing pulsatile GH release rather than the sustained elevation associated with CJC-1295 with DAC.
  • It serves as a research counterpart to sermorelin and as a comparator to CJC-1295 with DAC in GHRH-axis pharmacology.
  • It is commonly studied in combination with ghrelin-receptor agonists for synergistic GH release in research models.
  • Mod GRF 1-29 is not an FDA-approved drug.

References

  1. 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.
  2. Frohman LA, Downs TR, Williams TC, et al. Rapid enzymatic degradation of growth hormone–releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus. J Clin Invest. 1986;78(4):906–913.

This article is provided for educational and research purposes only. Mod GRF 1-29 is a research peptide. It is not an approved drug or therapeutic agent and is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease or condition. All work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.

MOD-GRF-1-29 | BonesLabs