Modified GHRH(1-29) Analog
CJC-1295 is a synthetic 30-amino-acid analog of growth hormone-releasing hormone (GHRH), first developed by ConjuChem Biotechnologies (now Theratechnologies). The peptide is based on the truncated GHRH(1-29) sequence (Sermorelin) with four amino acid substitutions at positions 2, 8, 15, and 27 (Ala2, Gln8, Ala15, Leu27) that confer resistance to dipeptidyl peptidase IV (DPP-IV) enzymatic degradation — the primary mechanism of endogenous GHRH inactivation. CJC-1295 exists in two pharmacokinetically distinct forms that are critical to distinguish: CJC-1295 without DAC (also known as Modified GRF 1-29 or Mod GRF) has a half-life of approximately 30 minutes and preserves the physiological pulsatile pattern of GH release. CJC-1295 with DAC (Drug Affinity Complex) incorporates a reactive maleimido group that forms a covalent bond with serum albumin after injection, extending the half-life to approximately 8 days and producing continuous, non-pulsatile GH elevation. This pharmacokinetic dichotomy from a single peptide backbone makes CJC-1295 uniquely valuable for research: the no-DAC form enables study of amplified pulsatile GHRH signaling (how the body naturally controls GH), while the DAC form enables study of sustained tonic GHRH signaling (what happens when GH is chronically elevated). The 2006 study by Teichman et al. in the Journal of Clinical Endocrinology & Metabolism demonstrated that CJC-1295 with DAC produced sustained GH and IGF-1 elevation for up to 14 days following a single injection.
No-DAC preserves GH pulsatility (~30 min half-life); DAC provides sustained elevation (~8 day half-life) from the same peptide backbone.
Four strategic amino acid substitutions prevent enzymatic degradation, dramatically extending biological activity vs native GHRH.
No-DAC form combined with Ipamorelin or other GHRPs produces synergistically amplified GH pulses greater than either alone.
Both forms produce sustained IGF-1 increases, with DAC maintaining elevated IGF-1 for 7–14 days per injection.
Works through the body's own GHRH receptor — amplifies endogenous GH production rather than providing exogenous GH.
The two forms enable direct comparison of pulsatile vs tonic GH stimulation in otherwise identical research protocols.
CJC-1295 binds to the GHRH receptor (GHRH-R), a class B GPCR located on somatotroph cells in the anterior pituitary gland. Receptor binding activates Gαs-coupled adenylyl cyclase, increasing intracellular cAMP and activating PKA. This signaling cascade has two primary effects: acute GH vesicle exocytosis (release of pre-formed GH) and longer-term upregulation of GH gene transcription, increasing the pituitary's GH synthesis capacity. The no-DAC form preserves GHRH receptor sensitivity by mimicking the natural pulsatile GHRH pattern from the hypothalamus. Between pulses, GHRH-R resensitizes, allowing each subsequent dose to produce a robust GH pulse. This is the physiological pattern: GH is secreted in discrete pulses (6–12 per day) with the largest pulse occurring during early slow-wave sleep. The DAC form fundamentally alters this pattern. After subcutaneous injection, the maleimido group reacts with the free thiol of albumin's Cys34 residue, forming a stable thioether bond. This albumin-conjugated CJC-1295 circulates with albumin's ~19-day half-life (the peptide dissociates before albumin degrades, giving an effective ~8-day half-life). The result is continuous GHRH receptor stimulation, which produces sustained GH elevation but with progressively blunted pulses as the receptor desensitizes. This tonic GH elevation profile differs fundamentally from physiological pulsatility and is valuable for studying the biological differences between pulsatile and continuous GH signaling.
Direct comparison of physiological pulsatile GH (no-DAC) vs sustained tonic GH (DAC) using the same peptide backbone.
ActiveStudying restoration of youthful GH pulsatility in aging models using the no-DAC form with GHRPs.
ActiveDAC form provides sustained IGF-1 elevation for studying long-term IGF-1 signaling effects on tissue growth and metabolism.
ActiveCJC-1295's four substitutions serve as a model for engineering DPP-IV-resistant peptide analogs in other therapeutic contexts.
ActiveGH-mediated effects on lean mass, fat oxidation, and bone density through amplified endogenous GH production.
Preclinical| Period | Dose | Frequency | Notes |
|---|---|---|---|
| 1–4 (no DAC) | 100 mcg | 2–3× daily (SC) | Combine with Ipamorelin 200 mcg for synergistic GH pulse |
| 5–12 (no DAC) | 100 mcg | 2–3× daily (SC) | Maintenance — same timing as Ipamorelin (fasted, pre-sleep) |
| 1–4 (DAC) | 1 mg | Once weekly (SC) | Weekly injection for sustained GH/IGF-1 elevation |
| 5–12 (DAC) | 2 mg | Once weekly (SC) | Maximum studied dose — produces ~14 days of elevated IGF-1 |
CJC-1295 no-DAC (Mod GRF 1-29) has a ~30-minute half-life and preserves physiological GH pulsatility. CJC-1295 with DAC has a reactive maleimido group that covalently binds to serum albumin, extending the half-life to ~8 days and producing continuous (non-pulsatile) GH elevation. The no-DAC form is preferred for research requiring natural GH pulse patterns; the DAC form is used when sustained, continuous GH signaling is the objective.
The no-DAC form is more commonly used because it preserves physiological GH pulsatility and pairs synergistically with GHRPs like Ipamorelin. The DAC form is more convenient (once weekly vs 2–3 times daily) but produces tonic GH elevation that may lead to GHRH receptor desensitization. Choose based on whether your research question requires pulsatile or sustained GH stimulation.
The standard protocol uses CJC-1295 no-DAC (100 mcg) + Ipamorelin (200 mcg) injected simultaneously, subcutaneously, 2–3 times daily. Optimal timing: morning (fasted), post-exercise, and pre-sleep. They can be mixed in the same syringe. The combination produces synergistic GH pulses: CJC-1295 primes somatotrophs via GHRH-R (increasing GH production and vesicle loading), and Ipamorelin triggers release via GHS-R1a.
No — CJC-1295 works through the pituitary's own GHRH receptor, amplifying endogenous GH production. This is fundamentally different from exogenous GH (HGH), which suppresses endogenous production via negative feedback. However, the DAC form's continuous GHRH-R stimulation may cause some receptor desensitization over time, potentially reducing GH pulse amplitude. This is not seen with the no-DAC form's intermittent dosing.
Reconstitute lyophilized CJC-1295 (either form) with bacteriostatic water at 2 mg/mL. For a 2 mg vial, add 1 mL BAC water. Inject slowly against the vial wall, swirl gently. Store at 2–8°C and use within 21 days. Do not shake or freeze. The solution should be clear and colorless.
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