GHRH receptor agonist (long-acting; albumin-conjugating)
CJC-1295 DAC
Modified GRF(1-29) covalently conjugated to a maleimidopropionic acid (MPA) linker — 'Drug Affinity Complex'
Overview
CJC-1295 DAC and CJC-1295 No DAC share an identical peptide backbone: the same Modified GRF 1-29 sequence with the same four amino acid substitutions at positions 2, 8, 15, and 27. What distinguishes them is a single additional chemical group — a maleimidopropionic acid (MPA) linker attached to the C-terminus of the peptide. That one addition, the 'Drug Affinity Complex,' is the entire editorial story.
The MPA linker's function is to seek out and covalently bind free cysteine-34 residues on serum albumin after subcutaneous injection. Albumin is the most abundant protein in blood plasma and has a native half-life of about three weeks. Anything covalently attached to albumin inherits a fraction of that circulation time. In CJC-1295 DAC's case, the pharmacokinetic result is a half-life extension from ~30 minutes to approximately 8 days — over 300-fold — from a chemical modification that adds less than 5% to the molecule's mass.
The important observation is that this doesn't just make the same drug last longer. It makes a different drug. Short-acting GHRH analogues (sermorelin, tesamorelin, CJC-1295 No DAC) produce pulsatile GH release because their circulating concentration falls fast enough between doses for the pituitary to reset. CJC-1295 DAC's concentration doesn't fall — it plateaus. What that produces is not a bigger pulse but a sustained low elevation. Ionescu JCEM 2006 showed, surprisingly, that pulsatile GH release from the pituitary still persists under this sustained GHRH-receptor stimulation, but the average GH exposure and the downstream IGF-1 profile are fundamentally different from what a pulsatile secretagogue produces.
Quick Facts & Evidence
- Category
- GHRH receptor agonist (long-acting; albumin-conjugating)
- Research area
- GHRH analogue
- Most studied for
- GH-axis pharmacology research (sustained receptor occupancy)
- Pulsatile-GH-under-continuous-stimulation research (Ionescu 2006)
- Comparison studies with short-acting GHRH analogues
- Clinical status
- Research use only — no approved clinical indication
- Human evidence
- Moderate Human Evidence
- Regulatory status
- Not approved by FDA, EMA or MHRA
Moderate Human Evidence
Supported by human trials, but of limited size, duration, or replication. May be approved for related but not identical indications.
Research Protocols
Research Protocol Snapshot
Preparation covered on this page
Freeze-dried injectable research format
This page covers the RUO lyophilized CJC-1295 DAC vial reconstituted with bacteriostatic water for subcutaneous research use, following the standard Healthy Mango preparation convention.
CJC-1295 DAC research values at a glance.
| Item | Example value |
|---|---|
| Vial size | 5 mg |
| Liquid used to mix | Bacteriostatic water |
| Amount of liquid added | 2.0 mL |
| Final concentration | 2.5 mg/mL |
| How it's given | Subcutaneous injection |
| Research dose | 1–2 mg per injection |
| Frequency | 1× per week OR 1× per 2 weeks — never 5×/week |
| After mixing | Refrigerate; use within 7–10 days |
Reported Dosing
The practitioner-reference research protocol for CJC-1295 DAC is 1–2 mg per subcutaneous injection, once per week or once per two weeks. It is educational reference, not a recommendation.
The Reported Protocol
| Dose | Frequency | Duration | Notes |
|---|---|---|---|
| 1–2 mg | 1× per week or 1× per 2 weeks, subcutaneous | 3 months on / 1 month off | 0.4–0.8 mL at 2.5 mg/mL |
Why protocols vary
The DAC modification (drug affinity complex) binds serum albumin and extends the plasma half-life to approximately 8 days. That accumulation is what allows once-weekly (or once-every-two-weeks) dosing.
This form is NEVER used on the 5×/week No-DAC schedule. The 8-day half-life means daily or every-other-day dosing accumulates to supraphysiologic GH levels by week two. That is a genuine safety-relevant distinction and the Peptide Guide flags it explicitly.
Preparing the Solution
Turning the freeze-dried powder into a measurable liquid.
Documented preparation
The documented research protocol is based on this preparation concentration.
Freeze-dried powder: 5 mg vial
Diluent: 2.0 mL bacteriostatic water
Final concentration: 2.5 mg/mL
Vial and volume from the practitioner reference; concentration calculated · Research-practitioner guide
Your vial
Matching preparation
Bacteriostatic water
2mL
Resulting concentration
2.5 mg/mL
Equivalent volume
The reported research amount of 1–2 mg is contained within
0.4–0.8mL
of the prepared solution now in your vial.
Show calculation
- Documented concentration
- 5 mg ÷ 2 mL = 2.5 mg/mL
- Bacteriostatic water to match the documented concentration
- 5 mg ÷ 2.5 mg/mL = 2 mL
- Equivalent volume at this concentration
- 1–2 mg ÷ 2.5 mg/mL = 0.4–0.8 mL
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.
This tool performs arithmetic conversions using the preparation example and reported research amount shown on this page. It does not recommend an amount, route, preparation method, or use.Sources for these values
- Documented in the practitioner referenceResearch-practitioner guide
This example explains how concentration and volume are calculated for the standard RUO preparation. It is not a preparation guide.
How It's Given
Method used for this format
Subcutaneous injection, 1× per week or 1× per 2 weeks
Documented in the practitioner reference · Research-practitioner guide
Why this method
CJC-1295 DAC is a modified 30-amino-acid peptide; the subcutaneous route delivers it into circulation without the gastrointestinal degradation that would break the molecule down.
The weekly (or fortnightly) cadence matches the ~8-day half-life. Higher-frequency schedules accumulate serum drug concentration and produce sustained supraphysiologic GH elevation rather than a physiologic pulse.
Injection sites reported
- Abdomen (rotate sites)
- Front of the thigh
- Avoid scarred, bruised, inflamed, or infected skin
Storage
Before mixing
- Refrigerate 2–8 °C
- Protect from light
- Do not freeze
Documented in the practitioner reference; general RUO practice · Research-practitioner guide
After mixing
- Refrigerate 2–8 °C
- Use within 7–10 days
- Do not freeze
- Discard if cloudy or discoloured
Documented in the practitioner reference · Research-practitioner guide
Handling
- Direct diluent slowly down the vial wall
- Gently swirl until dissolved — do not shake
- New sterile needle each draw
- Do not share vials
General RUO practice · Research-practitioner guide
Storage guidance summarises documented practitioner practice and standard RUO peptide handling. Verify the specific vial's supplied instructions before use.
Common Cycle
The practitioner-reference cadence is a 3-month active cycle followed by a 1-month washout — a duration chosen to prevent pituitary receptor desensitisation.
- Cycle Length
- 3 months on
- Break Before the Next Cycle
- 1-month washout between cycles
- What the Research Shows
- Not defined for grey-market use
Documented in the practitioner reference · Research-practitioner guide
Teichman 2006 and Ionescu 2006 are the peer-reviewed CJC-1295 DAC human phase-1 PK/PD studies. Both use short single-dose or multi-dose designs, not the on/off cadence above.
Compound Overview
Current areas of research
There is no approved indication for CJC-1295 DAC. The following are effects characterised in the Teichman and Ionescu phase-1 programs and in mechanistic research.
- Sustained GHRH-receptor stimulation across the dosing interval (Teichman 2006)
- Dose-related IGF-1 elevation persisting across the ~1-week dosing interval
- Preserved pulsatile GH release from the pituitary even under continuous receptor stimulation (Ionescu 2006) — a finding about somatotroph biology, not about clinical benefit
- Practical convenience of weekly rather than daily administration
Mechanism of action
CJC-1295 DAC and CJC-1295 No DAC share an identical peptide backbone: the same Modified GRF 1-29 sequence with the same four amino acid substitutions at positions 2, 8, 15, and 27. What distinguishes them is a single additional chemical group — a maleimidopropionic acid (MPA) linker attached to the C-terminus of the peptide. That one addition, the 'Drug Affinity Complex,' is the entire editorial story.
The MPA linker's function is to seek out and covalently bind free cysteine-34 residues on serum albumin after subcutaneous injection. Albumin is the most abundant protein in blood plasma and has a native half-life of about three weeks. Anything covalently attached to albumin inherits a fraction of that circulation time. In CJC-1295 DAC's case, the pharmacokinetic result is a half-life extension from ~30 minutes to approximately 8 days — over 300-fold — from a chemical modification that adds less than 5% to the molecule's mass.
The important observation is that this doesn't just make the same drug last longer. It makes a different drug. Short-acting GHRH analogues (sermorelin, tesamorelin, CJC-1295 No DAC) produce pulsatile GH release because their circulating concentration falls fast enough between doses for the pituitary to reset. CJC-1295 DAC's concentration doesn't fall — it plateaus. What that produces is not a bigger pulse but a sustained low elevation. Ionescu JCEM 2006 showed, surprisingly, that pulsatile GH release from the pituitary still persists under this sustained GHRH-receptor stimulation, but the average GH exposure and the downstream IGF-1 profile are fundamentally different from what a pulsatile secretagogue produces.
- The MPA linker is the whole story — one chemical addition, ~300-fold half-life extension, entirely different pharmacology
- Not a longer-lasting pulse: a sustained plateau in circulating drug and a sustained IGF-1 elevation across the ~1-week dosing interval
- The 'CJC-1295' human trials (Teichman 2006, Ionescu 2006) that most sources reference are actually about this molecule, not about No DAC
Human research
This is the compound page where Teichman JCEM 2006 and Ionescu JCEM 2006 belong. When general sources refer to 'CJC-1295 phase-1 data,' this is where those papers actually live. Teichman characterised the dose-response and half-life (~5.8 to 8.1 days depending on the specific cohort) in healthy adults, and demonstrated sustained GH and IGF-1 elevation across the dosing interval. This is the paper that establishes the ~8-day half-life often cited for 'CJC-1295' — it is a DAC number.
Ionescu 2006 is arguably the more scientifically interesting paper. It asked what happens to the pituitary's own pulsatile GH-release pattern when the GHRH signal is continuous rather than pulsatile. The finding was that pulsatility persists — the somatotroph's intrinsic dynamics generate a pulse rhythm even under a flat receptor-level input. That is a fundamental insight about pituitary biology, not just about this drug.
Evidence level is Level B (moderate). Mechanism is well characterised, human PK is well characterised, and the compound has published phase-1 safety data. What is absent is a modern controlled trial in any indication and any post-marketing surveillance dataset. The evidence base has been essentially frozen since 2006.
Teichman JCEM 2006
Phase-1 dose-ranging trial in healthy adults. Characterised the CJC-1295 DAC half-life (~5.8–8.1 days depending on dose cohort), the GH dose-response, and the sustained IGF-1 elevation across the ~1-week dosing interval. This is the source of the '8-day half-life' number that general sources attribute to 'CJC-1295' broadly.
Ionescu JCEM 2006
Investigated whether pulsatile GH release from the pituitary would persist under continuous GHRH-receptor stimulation with CJC-1295 DAC. The surprising finding: pulsatility persisted, indicating that GH pulse rhythm is generated by somatotroph-intrinsic dynamics rather than by pulsatility of the incoming GHRH signal. A fundamental somatotroph-biology finding.
Alba AJP-Endo 2006
Preclinical companion study in GHRH-knockout mice, showing once-daily CJC-1295 administration normalised growth. Supports the receptor-level mechanism across both DAC and No-DAC forms.
The most important piece of context for CJC-1295 DAC is that its commercial development ended abruptly. ConjuChem Biotechnologies, the Canadian company that developed both the DAC form and the No-DAC intermediate, took CJC-1295 DAC into phase-1 trials in the mid-2000s. Teichman JCEM 2006 and Ionescu JCEM 2006 are the published outputs of that program. Phase-2 was planned but never advanced substantially, and ConjuChem went into bankruptcy protection in 2011.
That leaves the compound in an unusual position: a peptide with published human PK/PD, characterised safety in a phase-1 population, and no active commercial development program under any sponsor. The Teichman and Ionescu papers remain the newest human clinical trial data on the molecule — nearly two decades later, no modern controlled trial has replaced them.
Contemporary access is via compounding pharmacies (where legally permitted) or research-supply channels. There is no post-marketing surveillance dataset, because the compound was never marketed. Framing on Healthy Mango is educational — the pharmacology is genuinely interesting and the Teichman/Ionescu papers deserve to be read on their own terms — not a recommendation for use.
Safety considerations
The following have been reported in the Teichman 2006 phase-1 program and in research-context observations. Sustained IGF-1 elevation is the mechanistic explanation for several of the tolerability differences from short-acting GHRH analogues.
- Injection-site reactions — Reported in Teichman 2006
- Water retention — More pronounced than with short-acting GHRH analogues, attributable to sustained exposure
- Joint pain and stiffness — Class-typical GH signal effect, more pronounced with sustained IGF-1
- Paresthesia (carpal tunnel-like symptoms) — Reported with sustained IGF-1 elevation
- Facial flushing — Class-typical GHRH effect, typically transient after injection
- Headache
- Elevated fasting glucose — Attributable to sustained IGF-1 and GH exposure; monitor in participants with prediabetes
There is no approved-label list of contraindications because development did not reach approval. The following draws on the general GHRH-analogue class safety profile and the specific pharmacokinetic consideration of sustained exposure.
- Disruption of the hypothalamic-pituitary axis (hypophysectomy, hypopituitarism, pituitary tumour surgery, head irradiation, head trauma)
- Active malignancy (theoretical risk from sustained IGF-1 elevation is higher than with pulsatile GHRH analogues)
- Pregnancy
- Known hypersensitivity to GHRH-related peptides
- Not appropriate for concurrent use with rhGH replacement — exposures accumulate
- Sustained IGF-1 elevation warrants closer monitoring in diabetes or prediabetes than a pulsatile GH secretagogue would
Monitoring
- IGF-1 at baseline and periodically — sustained elevation matters more than the pulsatile equivalent
- Fasting glucose and HbA1c in participants with diabetes or prediabetes
- Signs of fluid retention (weight, peripheral oedema)
- New-onset joint pain or paresthesia (indicators of IGF-1 running above the age-appropriate range)
- Injection-site reactions across rotation sites
Frequently asked questions
What does the MPA linker actually do?
Maleimidopropionic acid (MPA) is a short chemical linker with a maleimide group that reacts covalently with free thiol groups. Serum albumin has one accessible free thiol — cysteine-34 — that is present in almost every albumin molecule circulating in blood. After subcutaneous injection, the MPA-labelled peptide finds cysteine-34, forms a covalent bond, and travels with the albumin molecule for the remainder of albumin's lifecycle. Because albumin has a ~3-week native half-life, anything bound to it inherits a substantial fraction of that circulation time. That is the entire mechanism by which the ~30-minute peptide becomes an ~8-day drug.
If DAC lasts 8 days, why is the pulse pattern different from a bigger pulse?
This is the interesting pharmacologic point. A bigger, longer pulse would still be a pulse — the GHRH signal would rise, GH release would spike, and then both would fall. That is what a higher dose of sermorelin or CJC-1295 No DAC produces. DAC is different because the signal doesn't fall between doses. The GHRH-receptor sees a sustained input, and the average GH exposure is elevated across the entire dosing interval. Ionescu 2006 found that the somatotroph still generates pulses of GH release on top of that sustained elevation — but the baseline is raised. The result is not 'more of what No DAC does' but a fundamentally different exposure pattern.
Why is dosing weekly rather than daily?
Because the ~8-day half-life makes daily dosing produce steady-state accumulation with no additional benefit. By day seven of daily dosing, drug from six earlier doses is still substantially present in circulation. The Teichman 2006 phase-1 program tested weekly and every-other-week schedules for exactly this reason. Daily dosing of CJC-1295 DAC is the single most consequential error in the space, and its adverse consequences (severe water retention, sustained IGF-1 above age-appropriate range, joint pain, headache) are documented in the online research community.
Why did ConjuChem never bring CJC-1295 DAC to market?
ConjuChem's DAC platform was an interesting technology in principle — the albumin-binding trick can be applied to many peptide drugs, not just GHRH analogues — but the company faced commercial and financing difficulties throughout the late 2000s. Phase-2 development of CJC-1295 DAC was planned but never advanced substantially, and ConjuChem entered bankruptcy protection in 2011. The compound has not had a subsequent commercial sponsor. The lack of a modern controlled trial does not reflect a scientific failure of the compound; it reflects a commercial trajectory that ended.
How is CJC-1295 DAC different from CJC-1295 No DAC pharmacologically?
Same receptor, same peptide backbone, same four amino acid substitutions. The MPA linker is the only chemical difference. But the pharmacologic outcomes are quite different: No DAC produces a ~30-minute pulse and requires daily dosing; DAC produces an ~8-day plateau and dosing is weekly. IGF-1 elevation is pulsatile-tracking-pulsatile with No DAC, and sustained with DAC. Water retention, joint pain, and paresthesia are more pronounced with DAC because sustained IGF-1 exposure is what drives them. The two forms are best thought of as different drugs with a shared molecular ancestry.
References
- [1]
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 — Teichman SL, Neale A, Lawrence B, et al., Journal of Clinical Endocrinology & Metabolism (2006)
- [2]
Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog — Ionescu M, Frohman LA, Journal of Clinical Endocrinology & Metabolism (2006)
- [3]
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse — Alba M, Fintini D, Sagazio A, et al., American Journal of Physiology - Endocrinology and Metabolism (2006)
- [4]
Peptides & Compounds — The No-Jargon Guide (v5) — Healthy Mango Editorial, Healthy Mango practitioner reference (2026)
Laboratory Reference Notice
This section summarizes procedures and study parameters reported in published scientific literature and laboratory protocols. It is provided for educational and research reference only and must not be interpreted as medical advice, clinical guidance, or instructions for personal use.
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