CJC-1295 No DAC Peptide (10MG)

There is no published study of Modified GRF (1-29) on its own. Rather than attach this page to a study of a different peptide, it traces where the tetrasubstituted sequence came from and names the evidence gap directly.

Each of the four substitutions was introduced for a documented reason, and the assembled sequence appears in the published literature as the peptide core of CJC-1295. What has not been published is a characterization of the unconjugated peptide by itself.

Scope: The sources below are in vitro work, rat studies and the patent record. None of them tested Modified GRF (1-29) as sold, and none establishes effects, safety or dosing in people.

Growth hormone-releasing factor is a 44-amino-acid hypothalamic peptide. Wehrenberg and Ling (1983) reported that the N-terminal 1-29 fragment retains essentially the biological potency of the full-length molecule, which is why nearly all synthetic GRF analogs are built on the 1-29 scaffold. That unmodified fragment is also known as sermorelin.

Native hGRF (1-29) is cleared rapidly. Frohman (1986) identified the main route: dipeptidyl peptidase-IV cleaves the peptide near the N-terminus, between positions 2 and 3, producing a biologically inactive product. Substitutions at position 2 are a direct response to that finding.

Position 2, L-Ala to D-Ala. Changing the position-2 residue to the D-isomer blocks the dipeptidyl peptidase-IV cleavage that Frohman (1986) described as the principal inactivation route for GRF in plasma. This substitution is about resistance to enzymatic degradation, not receptor affinity.

Position 8, Asn to Gln. Felix and Heimer's patent (US 5,846,936, priority 1991, granted 1998) states that replacing asparagine at position 8 "prevents the slow deamidation of asparagine to the biologically inactive isoaspartic acid." This is chemical shelf stability, not enzymatic stability. Gln is one of several listed replacements.

Position 15, Gly to Ala. Coy, Hocart and Murphy (1991) reported that this substitution made the analog about 5 times more potent than the Gly-15 parent in rat pituitary cell cultures. Alanine favors α-helix formation, and the authors attributed the gain to a more stable amphiphilic α-helix at the receptor. This is the one substitution with a published potency figure attached.

Position 27, Met to Leu. The same Felix and Heimer patent states that replacing methionine at position 27 "prevents the oxidation of methionine to methionine sulfoxide." Again a chemical stability measure, protecting the peptide during synthesis and storage.

Two of the four changes (positions 8 and 27) exist to keep the molecule intact on the shelf. One (position 2) exists to slow enzymatic breakdown. Only one (position 15) was introduced to increase potency at the receptor.

The complete tetrasubstituted sequence appears in Jetté et al. (2005) in Endocrinology, the paper that identified CJC-1295.

The researchers made three maleimido derivatives of hGRF (1-29) and conjugated them to serum albumin:

• CJC-1288: hGRF (1-29) with an added lysine at position 30 carrying the maleimide
• CJC-1293: the same, plus D-Ala at position 2
• CJC-1295: the tetrasubstituted sequence (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) with the maleimide on the C-terminal lysine

All three conjugates showed greater resistance to dipeptidyl peptidase-IV in vitro and stimulated GH secretion in cultured rat anterior pituitary cells. After subcutaneous administration in male Sprague Dawley rats, all three produced acute GH release. CJC-1295 performed best, with about a 4-fold greater GH area under the curve over 2 hours than unmodified hGRF (1-29). It remained detectable in plasma beyond 72 hours, and Western blots showed it on the albumin band from 15 minutes onward.

Important distinction: every result above is for the albumin-conjugated molecule. The conjugation is what produced the extended plasma presence. Those findings do not transfer to the unconjugated peptide, which by design lacks the linker that drives them.

No published study characterizes unconjugated [D-Ala², Gln⁸, Ala¹⁵, Leu²⁷]hGRF (1-29)NH₂ on its own. Specifically, the literature does not provide:

• A potency figure for the assembled tetrasubstituted sequence in a receptor or pituitary cell assay
• Plasma stability or clearance data for the unconjugated peptide
• A head-to-head comparison against unmodified hGRF (1-29) or against sermorelin
• Any in vivo study in which the unconjugated peptide was the test article

Potency figures that circulate for this compound generally come from one of two sources that do not describe it: the 49-fold figure from Coy et al. (1991), which belongs to a different analog ([D-Ala², Ala⁸,⁹,¹⁵]GRH (1-29)NH₂), or the CJC-1295 data from Jetté et al. (2005), which belong to the albumin conjugate.

Because this paper is often cited on pages about Modified GRF (1-29), it is worth stating precisely what it covered.

Coy, Hocart and Murphy tested a series of GRH (1-29)NH₂ analogs with alanine substitutions in rat pituitary cell monolayers, measuring GH release against an unmodified GRH (1-29)NH₂ standard. Reported potencies included about 5-fold for [Ala¹⁵], about 4-fold for [Ala⁸], about 15-fold for [Ala⁸,¹⁵], about 27-fold for [D-Ala², Ala⁸,¹⁵], and about 49-fold for [D-Ala², Ala⁸,⁹,¹⁵], the most potent analog in the series.

The study supports the Ala¹⁵ substitution used in Modified GRF (1-29). It did not test Gln⁸ or Leu²⁷ in an agonist analog, and it did not test the Modified GRF (1-29) sequence. Leu²⁷ appears in the paper only within its antagonist series, which inhibits rather than stimulates GH release.

• The provenance above is assembled from several sources, each with its own methods and limitations. It is not a single characterization of one compound.
• Coy et al. (1991) measured GH release in cultured rat pituitary cells, a system the authors noted reflects receptor affinity rather than how a peptide behaves in a living animal.
• Jetté et al. (2005) tested albumin conjugates in rats. Its findings describe those conjugates.
• The patent record documents the intent behind the position 8 and 27 substitutions. It is not peer-reviewed evidence of their effect on potency.
• None of these sources establishes effects, safety or dosing in people.

Modified GRF (1-29) is a tetrasubstituted analog of hGRF (1-29) whose four changes have documented purposes: enzymatic stability at position 2, chemical stability at positions 8 and 27, and increased receptor potency at position 15. The assembled sequence is the peptide core of CJC-1295, characterized by Jetté et al. (2005) in its albumin-conjugated form in rats.

The unconjugated peptide has not been separately characterized in the published literature. Researchers evaluating this compound should treat potency and stability figures attributed to it with caution and check whether the figure belongs to a different analog or to the conjugated form.

This summary is provided for research and educational purposes. Statements on this page have not been evaluated by the FDA. Research compounds offered on this site are for laboratory research use only. They are not intended for human or veterinary use, or to diagnose, treat, cure, mitigate or prevent any disease.