CJC-1295 with DAC

CJC-1295 with DAC is a 30-residue synthetic analog of growth-hormone-releasing hormone. Its core is the tetrasubstituted GHRH(1-29) sequence — D-Ala2, Gln8, Ala15 and Leu27 in place of the native residues — to which a lysine carrying an Nε-3-maleimidopropionamide group has been added at the C-terminus. That maleimide is the Drug Affinity Complex (DAC). After the peptide enters the bloodstream the maleimide reacts covalently with the single free thiol on cysteine-34 of serum albumin, so the peptide circulates as an albumin conjugate and inherits albumin's multi-day residence time. It is important to distinguish this compound from the no-DAC product, often sold as Mod GRF 1-29, which is the same 29-residue core without the linker and has a half-life of minutes rather than days.

Origin and design

The compound was developed by ConjuChem (Montreal) as an application of its albumin-bioconjugation platform. Jetté et al. (2005) synthesised three maleimido derivatives of hGRF(1-29), showed that all three conjugated to human serum albumin, resisted dipeptidyl-peptidase-IV degradation in vitro and released GH from cultured rat pituitary cells, and selected the best candidate as CJC-1295. In rats it produced a four-fold larger GH area under the curve over two hours than unmodified hGRF(1-29), remained detectable in plasma beyond 72 hours, and Western blotting showed the immunoreactive peptide migrating with the albumin band within 15 minutes of injection [1]. The four core substitutions serve stability: D-Ala2 blocks the DPP-IV cleavage site, Gln8 removes a deamidation-prone asparagine, Ala15 stabilises the helix, and Leu27 replaces an oxidisable methionine.

Human pharmacokinetics and GH/IGF-1 response

Teichman et al. (2006) reported two randomised, placebo-controlled, double-blind ascending-dose studies in healthy adults aged 21–61, lasting 28 and 49 days. A single subcutaneous injection produced dose-dependent increases in mean plasma GH of 2- to 10-fold for six days or more and in mean IGF-1 of 1.5- to 3-fold for 9–11 days. The estimated half-life of CJC-1295 was 5.8 to 8.1 days. With repeated weekly or biweekly dosing, IGF-1 stayed above baseline for up to 28 days, with evidence of accumulation; no serious adverse reactions were reported in those studies [2]. Ionescu and Frohman (2006) then sampled GH every 20 minutes overnight before and one week after a single injection in healthy young men. GH pulsatility was preserved — pulse frequency and amplitude were unchanged — but trough GH rose 7.5-fold, mean GH by 46% and IGF-1 by 45%, implicating elevated basal secretion rather than bigger pulses as the driver of the IGF-1 response [3]. In GHRH-knockout mice, once-daily CJC-1295 for five weeks normalised body weight, length and femur/tibia length and increased pituitary GH mRNA, consistent with somatotroph proliferation [4].

The 2006 trial halt and regulatory position

In July 2006 ConjuChem stopped a 192-participant Phase II trial in HIV-associated visceral adiposity after a participant died at a study site; the company did not resume development, and CJC-1295 never progressed to approval [5]. In 2024 FDA reviewed CJC-1295 in all its forms (free base, acetate, and the DAC free base, acetate and trifluoroacetate) for the section 503A compounding bulks list. The agency's briefing document for the 4 December 2024 Pharmacy Compounding Advisory Committee proposed that none of the CJC-1295 substances be included, and the original nominations had been withdrawn by the nominators [6]. Separately, anti-doping laboratories have identified CJC-1295 in seized unlabelled preparations and developed detection methods, reflecting its status as a prohibited substance in sport [7].

What the research does not establish

The entire human dataset consists of short pharmacokinetic and endocrine studies in healthy adults, lasting weeks and measuring hormone levels. No published trial reports body-composition, strength, recovery or ageing outcomes for CJC-1295 with DAC. The Phase II lipodystrophy trial that would have provided efficacy data was terminated and its results were never published. Continuous albumin-bound GHRH stimulation is a pharmacological state without a physiological precedent, and the long-term consequences of sustained trough GH elevation and somatotroph proliferation [3][4] are unknown. FDA's 2024 proposal not to list the substance for compounding [6] reflects exactly this evidence gap. This material is supplied strictly for in-vitro laboratory research.

Format. Lyophilized powder in a sealed glass vial. The DAC maleimide is reactive toward free thiols, which is the basis of its albumin binding; keep the compound away from thiol-containing reagents (DTT, mercaptoethanol, cysteine-containing buffers) unless conjugation is intended.

Reconstitution. Reconstitute with bacteriostatic water, directing the stream against the glass wall rather than onto the powder cake, then swirl gently until dissolved — do not shake. Our reconstitution calculator converts vial mass and diluent volume into concentration and U-100 syringe units. Maleimides hydrolyse slowly in aqueous solution above neutral pH, so reconstituted solution should be used promptly rather than stored long-term.

Storage. Lyophilized vials are typically stored at −20 °C and protected from light. Reconstituted solutions are generally refrigerated at 2–8 °C and are less stable than the dry powder. Aliquot before freezing to avoid repeated freeze-thaw cycles.

Handling. Standard laboratory practice applies: appropriate PPE, aseptic technique when reconstituting, and disposal in line with your institution's procedures. For in-vitro laboratory research only — not for human or veterinary use.