CJC-1295 DAC 5mg

What is CJC-1295 DAC ?

CJC-1295 DAC (CJC-1295 with DAC) is supplied as a 5mg lyophilised powder. Its maleimide linker binds covalently to serum albumin, which is what stretches the half-life from minutes to days.

It is the tetrasubstituted hGRF(1-29) backbone extended by a thirtieth lysine, whose side-chain amine carries 3-maleimidopropionic acid. In modification nomenclature it is Nε30-maleimidopropionyl-[D-Ala2, Gln8, Ala15, Leu27]-Sermorelin-Lys30. DAC stands for Drug Affinity Complex. The maleimide reacts with Cys34 of serum albumin, the most abundant free thiol in plasma, and forms a covalent thioether conjugate. Teichman et al. (J Clin Endocrinol Metab, 2006) estimated its half-life in healthy adults at 5.8 to 8.1 days. It binds the GHRH receptor on pituitary somatotrophs.

CJC-1295 DAC Research Applications

• Albumin bioconjugation : in rats, CJC-1295 gave a 4-fold larger GH area under the curve than hGRF(1-29) over 2 hours. It stayed in plasma beyond 72 hours (Jetté et al., 2005).
• Human pharmacology : after a single dose in healthy adults, mean plasma GH rose 2- to 10-fold for 6 days or more. IGF-I rose 1.5- to 3-fold for 9 to 11 days (Teichman et al., 2006).
• Pulsatility : GH pulse frequency and magnitude were unchanged, while trough GH rose 7.5-fold (Ionescu and Frohman, 2006).
• Knockout models : in GHRH knockout mice, daily CJC-1295 maintained normal body weight and length, and somatotroph proliferation was seen (Alba et al., 2006).

CJC-1295 DAC is studied in endocrine research on GHRH receptor pharmacology, somatotroph biology and sustained versus intermittent receptor stimulation. Albumin conjugation turns a minutes-long agonist into a multi-day one without changing how it binds the receptor.

CJC-1295 DAC vs CJC-1295 No DAC (Modified GRF 1-29)

The two share the same receptor and the same first 29 residues. Everything that separates them sits at the C-terminus. CJC-1295 without DAC, sold as modified GRF (1-29), stops at residue 29: C₁₅₂H₂₅₂N₄₄O₄₂, 3367.9 g/mol, with a half-life of the order of 30 minutes. CJC-1295 with DAC adds Lys30 carrying 3-maleimidopropionic acid, taking the mass to 3647.2 g/mol. The 279.3 difference is one lysine plus one maleimidopropionyl group, which makes mass the simplest check that a vial holds the DAC form.

Choose the no-DAC form when you need short, controllable exposure. Choose the DAC form when sustained receptor occupancy is the variable under study.

Research Overview

CJC-1295 DAC is a 30-residue growth hormone releasing hormone analogue carrying a maleimide group that binds covalently to serum albumin in circulation, molecular formula C₁₆₅H₂₆₉N₄₇O₄₆, molecular weight 3647.2 g/mol, CAS 863288-34-0. In modification nomenclature it is Nε30-maleimidopropionyl-[D-Ala2, Gln8, Ala15, Leu27]-Sermorelin-Lys30, that is the tetrasubstituted hGRF(1-29) backbone extended by a thirtieth residue, lysine, whose side-chain amine carries 3-maleimidopropionic acid. DAC stands for Drug Affinity Complex, and it is the entire reason cjc 1295 dac and cjc dac are searched separately from the no-DAC compound. A maleimide is a Michael acceptor, and the most abundant free thiol in plasma is Cys34 of human serum albumin, so the peptide forms a stable covalent thioether conjugate with albumin after administration rather than binding it reversibly. Jetté and colleagues (Endocrinology, 2005) synthesised three maleimido hGRF(1-29) derivatives, bioconjugated them to albumin and identified CJC-1295 as the long-lasting analogue; Teichman and colleagues (J Clin Endocrinol Metab, 2006) reported a terminal half-life of roughly 6 to 8 days in healthy adults. The four backbone substitutions each remove a degradation liability of native GRF(1-29): D-Ala2 blocks dipeptidyl peptidase-4 cleavage at the Tyr1-Ala2 bond, Gln8 removes an asparagine deamidation site, Leu27 removes a methionine oxidation site, and Ala15 is associated with increased potency. One widely repeated claim about the DAC form is contradicted by the literature. Ionescu and Frohman (J Clin Endocrinol Metab, 2006) reported that pulsatile GH secretion persisted during continuous GHRH-receptor stimulation by CJC-1295, indicating that pulse generation is not set by GHRH pulse frequency alone. Alba and colleagues (Am J Physiol Endocrinol Metab, 2006) examined the analogue in the GHRH knockout mouse.

Storage and Reconstitution

Store the sealed 5mg vial at -20°C, dry and away from light. Keep reconstituted solution refrigerated at 2-8°C and freeze single-use aliquots for longer holding. Avoid repeated freeze-thaw cycles and prolonged storage of dilute solution at raised pH. Alkaline conditions hydrolyse the maleimide to an unreactive maleamic acid, which destroys the albumin-binding chemistry while the peptide backbone still looks intact by HPLC.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

Let the vial reach room temperature. Run bacteriostatic water slowly down the inside wall of the vial and swirl gently until clear and colourless. Do not shake or vortex. Keep free thiols out of the preparation: dithiothreitol, beta-mercaptoethanol, free cysteine and reduced glutathione all react with the maleimide. Label the vial with the reconstitution date and refrigerate it.

• Allow the vial to reach room temperature before opening so condensation does not settle on the powder.
• Keep thiols out of the system. The maleimide is a reactive Michael acceptor and will be consumed by any free sulfhydryl in the preparation, so dithiothreitol, beta-mercaptoethanol, free cysteine, reduced glutathione and thiol-containing buffer additives will quench the DAC function even though the peptide backbone appears intact by HPLC.
• Avoid alkaline conditions during reconstitution and storage. Maleimide hydrolyses to the unreactive maleamic acid at elevated pH, which is the quietest way to lose the albumin-conjugating chemistry that distinguishes this compound from the no-DAC form.
• Repeated freeze-thaw cycling degrades GHRH analogue peptides.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• hGRF(1-29)-albumin bioconjugates activate the GRF receptor, identification of CJC-1295 as a long-lasting GRF analog (Jetté et al., Endocrinology, 2005)
• Prolonged stimulation of GH and IGF-I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults (Teichman et al., J Clin Endocrinol Metab, 2006)
• Pulsatile secretion of growth hormone persists during continuous stimulation by CJC-1295 (Ionescu and Frohman, J Clin Endocrinol Metab, 2006)
• Once-daily CJC-1295 normalizes growth in the GHRH knockout mouse (Alba et al., Am J Physiol Endocrinol Metab, 2006)

Published research on CJC-1295 DAC is indexed on PubMed. See our full UK buyer's guide for CJC-1295 and UK buyer's guide for CJC-1295 CoA.