— Research note —
CJC-1295 with DAC
Long-acting GHRH analog incorporating a drug affinity complex for albumin binding, investigated for sustained growth hormone axis activation.
CJC-1295 with DAC is a 30-amino-acid synthetic analog of growth hormone-releasing hormone (GHRH) developed by ConjuChem in the early 2000s. The peptide incorporates four amino-acid substitutions in the GHRH(1-29) backbone (D-Ala at position 2, Gln at position 8, Ala at position 15, and Leu at position 27) to enhance enzymatic stability, along with a maleimidopropionic acid moiety at the C-terminus that constitutes the drug affinity complex (DAC). The DAC reacts covalently with cysteine-34 of circulating albumin in vivo, generating a long-lived albumin conjugate with an estimated plasma half-life of one to two weeks.
The DAC strategy was developed as a generalizable platform for prolonging the half-life of short-lived peptide hormones, and CJC-1295 served as an early proof-of-concept molecule. The expected pharmacodynamic profile of sustained GHRH receptor agonism produces a sustained, modest elevation of growth hormone and downstream insulin-like growth factor 1 (IGF-1) levels in preclinical research, distinguishing the molecule from short-acting GHRH analogs such as sermorelin or modified GRF (1-29).
Phase 1 and phase 2 clinical research conducted by ConjuChem in the mid-2000s reported sustained IGF-1 elevations with weekly subcutaneous dosing in healthy research volunteers. The clinical development program was subsequently discontinued, and the molecule has since circulated primarily as a research-chemical tool for academic and industry investigations of growth hormone axis pharmacology.
CJC-1295 with DAC is supplied here for laboratory research use only and is not intended for human consumption. The compound provides a tractable probe for studies of sustained GHRH receptor signaling, somatotroph adaptation, and the broader concept of albumin-conjugate peptide pharmacology.
Mechanism
CJC-1295 with DAC binds the GHRH receptor, a class B G-protein coupled receptor expressed on pituitary somatotrophs. Receptor engagement activates Gas, elevates intracellular cAMP, and stimulates pulsatile growth hormone release. Unlike the native hormone, which is rapidly degraded by dipeptidyl peptidase-4 and other proteases, the modified peptide is resistant to proteolytic cleavage at the N-terminus due to the D-Ala substitution and other backbone modifications.
The DAC moiety at the C-terminus forms a covalent thioether bond with the free thiol of cysteine-34 on circulating serum albumin, generating an albumin-peptide conjugate that escapes renal filtration and proteolytic clearance. This produces sustained low-level GHRH receptor activation rather than the pulsatile pattern observed with short-acting analogs. The pharmacodynamic consequence is a sustained, modest elevation in growth hormone and IGF-1 levels, in contrast to the high-amplitude pulses generated by shorter-acting GHRH peptides.
Research history
ConjuChem developed the drug affinity complex platform in the late 1990s and early 2000s as a generalizable approach to extending the half-life of therapeutic peptides through covalent albumin conjugation. CJC-1295 (originally CJC-1295 DAC) emerged as an early flagship application of the platform to the GHRH-(1-29) scaffold.
Phase 1 studies published in 2005 and 2006 reported tolerability and dose-dependent IGF-1 elevations sustained over multiple weeks following single subcutaneous administration. A phase 2 study in HIV-associated lipodystrophy explored the molecule in body-composition endpoints. The development program was discontinued in the late 2000s following corporate restructuring at ConjuChem rather than for specific safety concerns.
The molecule subsequently entered the research-chemical market and has been studied in academic settings as a probe of sustained versus pulsatile GHRH receptor signaling. Investigators have used the compound to examine somatotroph adaptation to continuous receptor activation, downstream IGF-1 dynamics, and comparative pharmacology with shorter-acting GHRH analogs. Distinctions between CJC-1295 with DAC (the long-acting albumin-conjugate form) and CJC-1295 without DAC (the related modified GRF (1-29), which is a short-acting GHRH analog) are important to maintain in experimental design and interpretation.
References
- Teichman SL, et al. 2006. 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. PMID: 16332938
- Jette L, et al. 2005. hGRF1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. PMID: 15528308
- Ionescu M, Frohman LA. 2006. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. PMID: 17018653
- Sackmann-Sala L, et al. 2009. Activation of the GH/IGF-1 axis by CJC-1295 in a healthy young population. Growth Horm IGF Res.
- Alba M, et al. 2006. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. PMID: 16720627
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Information presented in third-person scientific context. Research use only. Not medical advice; not for human consumption.