What Is CJC-1295 No Dac?
Quick Answer
Research Overview CJC-1295 (no DAC), frequently referred to in the scientific literature as Modified GRF (1-29) or Mod GRF 1-29, is a synthetic peptide analog of endogenous growth hormone-releasing hormone (GHRH). It is derived from the first 29 amino acids of the native 44-amino acid GHRH molecule ...
Research Overview
CJC-1295 (no DAC), frequently referred to in the scientific literature as Modified GRF (1-29) or Mod GRF 1-29, is a synthetic peptide analog of endogenous growth hormone-releasing hormone (GHRH). It is derived from the first 29 amino acids of the native 44-amino acid GHRH molecule produced in the hypothalamus, representing the biologically active fragment responsible for stimulating growth hormone (GH) release from the anterior pituitary gland.[1][2] The peptide was originally developed by ConjuChem Biotechnologies Inc. (Montreal, Canada) as part of the CJC-1295 drug development program, where the tetrasubstituted core peptide served as the precursor to the long-acting DAC-conjugated variant.[4]
The term "tetrasubstituted" refers to four strategic amino acid substitutions in the native GHRH(1-29) sequence: D-Alanine at position 2, Glutamine at position 8, Alanine at position 15, and Leucine at position 27.[2][3] Each substitution serves a specific purpose: position 2 (D-Ala) prevents DPP-4 enzymatic cleavage, position 8 (Gln) reduces asparagine rearrangement or amide hydrolysis to aspartic acid, position 15 (Ala) enhances bioactivity, and position 27 (Leu) prevents methionine oxidation. These modifications collectively extend the half-life from the mere minutes characteristic of native GHRH to approximately 30 minutes for CJC-1295 (no DAC), dramatically improving bioavailability while preserving receptor binding characteristics.[1][5]
The "no DAC" designation is critically important for researchers to understand. CJC-1295 with DAC (Drug Affinity Complex) contains an N-epsilon-3-maleimidopropionyl-lysine linker that covalently binds to serum albumin, extending the half-life to 6–8 days and creating continuous, non-physiological GH stimulation.[4][8] In contrast, CJC-1295 (no DAC) lacks this conjugation entirely, producing pulsatile GH release that mimics the body's natural circadian rhythm. This pulsatile pattern is therapeutically preferred because it avoids receptor desensitization (downregulation) of GHRH receptors and minimizes side effects associated with chronic GH elevation.[5][6] The FDA, in its December 2024 Pharmacy Compounding Advisory Committee briefing, explicitly noted that many studies cited under the name "CJC-1295" actually utilized the DAC variant, and that no published human clinical trials or preclinical efficacy studies exist specifically for CJC-1295 without DAC.[9]
Research into CJC-1295 (no DAC) focuses on conditions driven by growth hormone deficiency (GHD) or age-related decline of the GH/IGF-1 axis. Key investigational areas include body composition and muscle hypertrophy (via GH-mediated protein synthesis and IGF-1 stimulation), lipid metabolism (GH-facilitated lipolysis and reduced visceral adipose tissue), tissue repair and injury recovery (collagen synthesis stimulation via the GH/IGF-1 axis), sleep physiology (GHRH analogs and slow-wave sleep enhancement), and anti-aging cellular function (restoring youthful GH pulsatility).[6][7][12] It is frequently studied in combination with Ipamorelin, a selective GH secretagogue that acts on a complementary receptor (the ghrelin/GHS receptor), for a synergistic effect on GH release.[12]
Forensic and analytical chemistry studies by Henninge et al. (2010) and Hartvig et al. (2014) have confirmed that products marketed as "CJC-1295" on the grey market frequently contain the no-DAC variant (Modified GRF 1-29) rather than the genuine CJC-1295 with DAC, underscoring the importance of precise nomenclature and rigorous analytical verification using RP-HPLC and LC-MS/MS.[1][3][13]
References
- Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Testing and Analysis, 2(11-12), 647-650, 2010.
- Soule S, King JA, Millar RP. Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men. The Journal of Clinical Endocrinology and Metabolism, 79(4), 1208-1211, 1994.
- Hartvig RA, Holm NB, Dalsgaard PW, Reitzel LA, Müller IB, Linnet K. Identification of peptide and protein doping related drug compounds confiscated in Denmark between 2007-2013. Scandinavian Journal of Forensic Science, 20(2), 42-49, 2014.
- Jetté L, et al. Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog. Endocrinology, 146(7), 3052-3058, 2005.
- Lance VA, Murphy WA, Sueiras-Diaz J, Coy DH. Super-active analogs of growth hormone-releasing factor (1-29)-amide. Biochemical and Biophysical Research Communications, 119(1), 265-272, 1984.
- Van Hout MC, Hearne E. Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions. Substance Use & Misuse, 51(1), 73-84, 2016.
- Sigalos JT, Pastuszak AW. The Safety and Efficacy of Growth Hormone Secretagogues. Sexual Medicine Reviews, 6(1), 45-53, 2018.
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. The Journal of Clinical Endocrinology & Metabolism, 91(3), 799-805, 2006.
- Food and Drug Administration. FDA Evaluation of CJC-1295 Related Bulk Drug Substances. FDA Briefing Document: Pharmacy Compounding Advisory Committee (PCAC) Meeting, December 4, 2024.
- Food and Drug Administration. Final Summary Minutes of the Pharmacy Compounding Advisory Committee Meeting. Center for Drug Evaluation and Research, December 4, 2024.
- World Anti-Doping Agency. The 2024 Prohibited List: International Standard. World Anti-Doping Code, 2024.
- Sinha DK, Balasubramanian A, Tatem AJ, Kovac JR, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational Andrology and Urology, 9(Suppl 2), S149-S159, 2020.
- Fabresse N, Grassin-Delyle S, Etting I, Alvarez JC. Identification of a GHRH peptide analogue, the CJC-1295, using LC-HRMS/MS. Toxicologie Analytique et Clinique, 29(2), 205-211, 2017.
- Ben-Shlomo A, et al. DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas. The Journal of Clinical Investigation, 130(11), 5738-5755, 2020.
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. The Journal of Clinical Endocrinology & Metabolism, 91(12), 4792-4797, 2006.
- Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Testing and Analysis, 13(11-12), 1871-1887, 2021.
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