Mod GRF 1-29: a forum name for a laboratory molecule

Where "1-29" comes from

Human growth-hormone-releasing hormone was not isolated from a human hypothalamus. It was isolated in 1982 from a pancreatic islet tumour that had been causing acromegaly, by Rivier, Spiess, Thorner and Vale, who characterised a 44-residue peptide and showed that its N-terminal 29 residues carried the full GH-releasing activity [Rivier et al., 1982]. That 29-residue piece, amidated at the C-terminus, became sermorelin: the first GHRH analogue to be marketed, as a diagnostic test at 1 µg/kg intravenously and as a paediatric treatment at 30 µg/kg subcutaneously once daily [Prakash et al., 1999].

Every molecule discussed on this site with "GRF" or "GHRH" in its description is a descendant of that fragment: sermorelin is the fragment itself, tesamorelin is the full 1-44 hormone with a protective group at the N-terminus, and CJC-1295 is the fragment with four swaps and a tail. The comparison of the three is drawn in sermorelin versus CJC-1295 ipamorelin.

What "modified" means: four swaps

The fragment's weakness is that it is cut quickly. The first two residues, tyrosine and alanine, are a substrate for dipeptidyl peptidase IV, and the chain has other cleavage sites further along. ConjuChem's answer, described in the paper that introduced CJC-1295, was a tetrasubstituted version of hGRF(1-29): D-alanine at position 2, glutamine at 8, alanine at 15, leucine at 27 [Jetté et al., 2005]. The D-amino acid at position 2 blocks the peptidase; glutamine at 8 replaces an asparagine prone to deamidation; alanine at 15 replaces a glycine to stiffen the helix; leucine at 27 replaces a methionine that oxidises. The result is the same length and the same receptor as sermorelin, with slower breakdown.

Swipe sideways to see the whole table.

In the ConjuChem paper this tetrasubstituted peptide is an intermediate: three maleimide derivatives were made from it and tested as albumin conjugates, and the best of them, with a maleimidopropionamide-lysine added at position 30, was named CJC-1295 [Jetté et al., 2005]. The tail is the "DAC"; what the tail was attached to is the molecule this page is about.

A forum name, not a paper

ConjuChem never developed the linker-free peptide as a product, so it never needed a name. When it reached the research-chemical market, sold alongside CJC-1295 proper, a way of telling the two apart was needed. "Modified GRF (1-29)", shortened to Mod GRF 1-29, was adopted on bodybuilding forums in the late 2000s and is now the name most suppliers use; "CJC-1295 without DAC" and "CJC-1295 no DAC" are the same thing said from the other direction.

The literature knows the molecule only as "the tetrasubstituted hGRF(1-29)" inside a 2005 methods section. A search for "mod grf 1-29" runs to about 480 queries a month in the United States; a search of CrossRef for the same phrase returns nothing.

That matters when reading claims. Any sentence of the form "studies show Mod GRF 1-29 does X" is borrowing from one of two neighbours: from sermorelin, the unmodified sequence, or from CJC-1295 with DAC, the linker-bearing product. The borrowing is reasonable for receptor pharmacology, since all three bind the same GHRH receptor, and unreasonable for pharmacokinetics, since the linker changes clearance by three orders of magnitude.

What is known, and from where

Receptor and effect. The GHRH receptor on the pituitary somatotroph, the same receptor sermorelin activates. The tetrasubstituted peptide was active in a GH secretion assay in cultured rat pituitary cells in the ConjuChem work, and its albumin conjugates were tested against it [Jetté et al., 2005].

Half-life. Not published in humans. The unmodified fragment is short-lived enough that Corpas and colleagues gave it subcutaneously twice a day for 14 days, and only the 1 mg dose, not 0.5 mg, significantly raised 24-hour GH, pulse amplitude and IGF-1 in ten men aged 68; at that dose their values no longer differed from those of nine men aged 26 [Corpas et al., 1992]. The four substitutions slow enzymatic cleavage, so Mod GRF 1-29 should last somewhat longer than sermorelin, but no one has measured by how much. The albumin-bound form, for contrast, has a measured half-life of 5.8 to 8.1 days [Teichman et al., 2006].

Human trials. None under this name. The GHRH-plus-GHRP synergy that motivates its pairing with a GHRP was shown with the full GHRH(1-44) and GHRP-6 in 1990 [Bowers et al., 1990]; the doses in that experiment, 1 µg/kg of GHRH and 0.1 to 1.0 µg/kg of GHRP-6, belong to those two molecules, not to this one. The dosage guide keeps that distinction.

Adverse effects. Unstudied for this peptide. The unmodified fragment's most frequent adverse events in the paediatric programme were transient facial flushing and injection-site pain [Prakash et al., 1999], and facial flushing of one to three minutes occurred in 16 of 18 men given GHRH(1-44) in Bowers' study [Bowers et al., 1990]. Flushing is a GHRH-receptor effect, so it is a fair expectation for any analogue.

Its place in the blend

The reason Mod GRF 1-29 exists as a market product is the blend. A GHRP such as ipamorelin triggers one GH pulse and is cleared within hours; the partner that raises the size of that same pulse has to arrive and leave on a similar clock. The linker-free peptide does; the albumin-bound one does not. The research-market vial therefore pairs Mod GRF 1-29 with ipamorelin, in equal mass, and a certificate for that vial must show a mass near 3,368 for the GHRH component. What a listing for that vial has to say is set out in CJC-1295 ipamorelin for sale.

Questions or corrections: editor@cjc-1295-ipamorelin.com. See the editorial policy.