— Research note —
MOD-GRF (CJC-1295 no DAC)
Stabilized 29-amino-acid GHRH analog (modified GRF 1-29) used in research as a short-acting probe of growth hormone secretion.
Modified GRF (1-29), commonly designated MOD-GRF or in research-chemical catalogs as "CJC-1295 without DAC," is a 29-amino-acid synthetic analog of the bioactive N-terminal fragment of growth hormone-releasing hormone (GHRH). The peptide incorporates four amino-acid substitutions relative to native GHRH (1-29) — D-Ala at position 2, Gln at position 8, Ala at position 15, and Leu at position 27 — that confer resistance to enzymatic degradation by dipeptidyl peptidase-4 and other plasma proteases, extending the in vivo half-life to approximately 30 minutes from the few minutes typical of the native sequence.
Unlike CJC-1295 with DAC, which incorporates a maleimidopropionic acid moiety that covalently binds serum albumin to produce a multi-week half-life, MOD-GRF lacks the albumin-binding modification. The resulting pharmacokinetic profile produces pulsatile GHRH receptor activation similar in duration to physiological GHRH release, which has made the molecule a useful research tool for studies that require short-acting, repeatable receptor stimulation rather than sustained activation.
In preclinical and early clinical research, MOD-GRF has been observed to elevate growth hormone and downstream IGF-1 levels in a pulsatile fashion that more closely approximates endogenous GHRH dynamics. Researchers have used the molecule in combination studies with growth hormone secretagogue receptor agonists (the ghrelin receptor family, including ipamorelin, GHRP-2, and GHRP-6) to investigate synergistic effects on growth hormone release, a phenomenon that reflects the dual-receptor regulation of somatotroph secretion.
The compound is supplied here for laboratory research use only and is not intended for human consumption. Its primary research utility lies in pituitary pharmacology, GHRH receptor signaling, and combination pharmacology studies with secretagogue receptor agonists.
Mechanism
MOD-GRF binds the GHRH receptor on pituitary somatotrophs, activating Gas, elevating intracellular cAMP, and stimulating release of stored growth hormone. The D-Ala substitution at position 2 protects against cleavage by dipeptidyl peptidase-4, the principal degradative enzyme for the native GHRH sequence. The additional substitutions at positions 8, 15, and 27 provide further proteolytic stability without altering receptor affinity.
The pharmacokinetic profile produces a relatively short receptor exposure of approximately 30 minutes, generating a single growth hormone pulse per dose rather than sustained receptor activation. This profile distinguishes MOD-GRF from the long-acting CJC-1295 with DAC and recapitulates aspects of physiological GHRH dynamics. When combined with ghrelin receptor agonists in research models, MOD-GRF produces synergistic growth hormone release, reflecting the complementary actions of GHRH (driving cAMP-dependent secretion) and ghrelin receptor signaling (mobilizing intracellular calcium through Gq).
Research history
The medicinal chemistry program at ConjuChem that produced CJC-1295 with DAC also generated the underlying modified GRF (1-29) backbone, which preceded conjugation with the albumin-binding moiety. The substitutions were rationalized from earlier work by Felix, Bowers, and others characterizing structure-activity relationships of GHRH analogs in the 1980s and 1990s.
The non-DAC form of the molecule has been used as a research tool since the early 2000s, with academic and industry investigators employing it to probe pulsatile growth hormone release and to test combination pharmacology with ghrelin receptor agonists. Studies from the Frohman and Bowers laboratories, among others, established the synergistic interaction between GHRH analogs and growth hormone secretagogues.
The compound has been compared with sermorelin (native GHRH 1-29 without modifications) and with tesamorelin (a different stabilized GHRH analog with N-terminal trans-3-hexenoyl modification). Each of these molecules engages the same receptor with similar potency but differs in pharmacokinetic profile, making them useful for distinct experimental questions. MOD-GRF continues to appear in research-chemical catalogs and academic publications as a reference probe for short-acting GHRH receptor agonism.
References
- Jette L, et al. 2005. hGRF1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats. Endocrinology. PMID: 15528308
- Bowers CY. 1996. Xenobiotic growth hormone secretagogues: growth hormone releasing peptides. In: Growth Hormone Secretagogues. Springer.
- Frohman LA, Kineman RD. 2002. Growth hormone-releasing hormone and pituitary development, hyperplasia and tumorigenesis. Trends Endocrinol Metab.
- Mayo KE, et al. 1995. Growth hormone-releasing hormone: synthesis and signaling. Recent Prog Horm Res. PMID: 7740160
- Sinha DK, et al. 2008. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition. Curr Drug Targets.
- Felix AM, et al. 1986. Synthesis, biological activity and conformational analysis of cyclic GRF analogs. Int J Pept Protein Res.
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Information presented in third-person scientific context. Research use only. Not medical advice; not for human consumption.