GHRH(1-29) Analogue with Drug Affinity Complex (Growth-Hormone Secretagogue, GRF Class)

CJC-1295

Also Known As: CJC-1295 with DAC, CJC-1295 without DAC, Modified GRF 1-29, Mod GRF(1-29), ModGRF 1-29, DAC:GRF, DAC-GRF, CJC-1295 DAC, CJC-1295 DAC-free

CJC-1295 is a synthetic, tetra-substituted analogue of residues 1–29 of human growth-hormone-releasing hormone (GHRH(1-29) / sermorelin) carrying the four substitutions D-Ala², Gln⁸, Ala¹⁵, and Leu²⁷ that stabilise the peptide against plasma DPP-IV cleavage. Two chemically distinct forms appear in the literature and must NOT be conflated: (a) CJC-1295 with DAC carries an additional C-terminal lysine (Lys³⁰) bearing an Nε-maleimidopropionyl group; once injected, the maleimide forms a covalent thioether bond with Cys³⁴ of human serum albumin in vivo, giving a half-life of roughly 6–8 days; (b) CJC-1295 without DAC, also called Modified GRF 1-29 / Mod GRF(1-29), has the same tetra-substituted backbone without the Lys³⁰ MPA extension and is short-acting (~30 min). ConjuChem advanced the with-DAC variant into clinical development; the only confirmed CJC-1295 study on ClinicalTrials.gov is NCT00267527 (Phase 2, HIV-associated visceral obesity), terminated on 17 July 2006 after the death of a participant at an Argentinian site (the on-site investigator attributed the death to asymptomatic coronary artery disease with plaque rupture, not to study drug). ConjuChem subsequently suspended the CJC-1295 programme in 2007–2008. CJC-1295 is NOT approved by the FDA, EMA, Health Canada, or any other major regulator; presence in research-chemical supply is not regulatory approval.

Identity & Chemistry

Peptide-sequence diagram of CJC-1295 with DAC, a 30-amino-acid tetra-substituted GHRH(1-29) analogue (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) extended by Lys³⁰ bearing an Nε-maleimidopropionyl group that covalently binds serum albumin.
Image credit: CMollerup, via Wikimedia Commons · CC BY-SA 4.0
Amino Acid Sequence
CJC-1295 with DAC (30 aa): Y-(D-A)-D-A-I-F-T-Q-S-Y-R-K-V-L-A-Q-L-S-A-R-K-L-L-Q-D-I-L-S-R-K(Nε-MPA)-NH₂ — D-Ala², Gln⁸, Ala¹⁵, Leu²⁷; C-terminal Lys³⁰ bears an Nε-maleimidopropionyl group that forms a covalent thioether with Cys³⁴ of human serum albumin in vivo (Drug Affinity Complex / DAC). CJC-1295 without DAC / Modified GRF 1-29 (29 aa): Y-(D-A)-D-A-I-F-T-Q-S-Y-R-K-V-L-A-Q-L-S-A-R-K-L-L-Q-D-I-L-S-R-NH₂ — same tetra-substituted backbone without the Lys³⁰ MPA extension.
Molecular Formula
C₁₆₅H₂₆₉N₄₇O₄₆ (CJC-1295 with DAC; PubChem CID 91971820) + C₁₅₂H₂₅₂N₄₄O₄₂ (CJC-1295 without DAC / Mod GRF 1-29; PubChem CID 91976842)
Molecular Weight
3647.25 g·mol⁻¹ (with-DAC free MPA-conjugate, before covalent albumin binding) + ~3367.9 g·mol⁻¹ (without-DAC / Mod GRF 1-29)
CAS Number
863288-34-0 (with DAC; supplier-canonical) / 446262-90-4 (with DAC; alternate registry, Wikipedia infobox) / 446036-97-1 (without DAC / Mod GRF 1-29)
PubChem CID
91971820
IUPAC Name
Nε³⁰-maleimidopropionyl-[D-Ala², Gln⁸, Ala¹⁵, Leu²⁷]-sermorelin-Lys³⁰ (concise form for the with-DAC variant; the parent sermorelin systematic name is documented at /portfolio/sermorelin). The without-DAC form lacks the Lys³⁰ MPA extension and is documented as Modified GRF 1-29. CJC-1295 has no canonical DrugBank monograph as of May 2026.
Solubility
Water-soluble; research-grade material is typically supplied as the acetate salt and reconstituted in bacteriostatic water or sterile 0.9% NaCl. Both forms are slightly soluble in DMSO (~1 mg/mL).
Storage
Lyophilised powder: store at −20 °C, protected from light. Reconstituted solution: short-term storage at 2–8 °C; avoid freeze-thaw cycles (per Cayman Chemical / ChemicalBook standards for each form).

Mechanism of Action

CJC-1295 is a GHRH(1-29) receptor agonist that activates the GHRH receptor (GHRHR) on pituitary somatotrophs. The with-DAC variant additionally binds covalently to serum albumin, extending the circulating half-life from minutes to days without abolishing physiological GH pulsatility.

The four substitutions D-Ala², Gln⁸, Ala¹⁵, and Leu²⁷ block DPP-IV cleavage of the N-terminal Tyr-Ala dipeptide and stabilise the backbone-exposed residues against further plasma proteolysis (Jetté et al. 2005). This gives the DAC-free variant (Modified GRF 1-29) a plasma half-life of roughly 30 minutes. The with-DAC variant additionally carries a C-terminal Lys³⁰ residue bearing an Nε-maleimidopropionyl group; once injected, the maleimide reacts with the free thiol of Cys³⁴ on circulating albumin to form a stable thioether conjugate that recycles via the FcRn salvage pathway and is cleared with the kinetics of albumin itself (terminal half-life ~5.8–8.1 days; Teichman et al. 2006). Pharmacodynamic placement within the GHRH analogue family: sermorelin (unmodified GHRH(1-29)) has t½ ~11–12 min; CJC-1295 without DAC ~30 min; tesamorelin (GHRH(1-44) with N-terminal trans-3-hexenoyl protection) ~26 min; CJC-1295 with DAC ~6–8 days. Despite continuous receptor stimulation, GH pulsatility is preserved: one week after a single subcutaneous 60–90 µg/kg injection, healthy adults retained pulse frequency and amplitude while trough GH rose ~7.5-fold and mean 12-h GH rose ~46% (Ionescu & Frohman, JCEM 2006).

Molecular Targets

  • GHRH receptor (GHRHR) — class B G-protein-coupled receptor on pituitary somatotrophs; primary target of both CJC-1295 forms
  • Human serum albumin (Cys³⁴) — covalent thioether bond via the Lys³⁰ Nε-maleimidopropionyl side chain is exclusive to the with-DAC variant (DAC technology)
  • No meaningful agonism at the ghrelin / GHS-R1a receptor (mechanistically distinct from GHRP-class secretagogues such as ipamorelin, GHRP-2, and GHRP-6)

Signaling Pathways

  • GHRHR → Gαs → adenylyl cyclase → ↑ cAMP → PKA → CREB phosphorylation → upregulation of the GH1 gene and exocytotic GH release; secondary Gαq/PLC arm at higher receptor occupancy
  • GH → hepatic GH receptor → JAK2/STAT5b → IGF-1 transcription and systemic anabolic / metabolic effects
  • Albumin-mediated half-life extension via the FcRn salvage pathway — exclusive to the with-DAC variant; clearance kinetics of the conjugate match those of albumin (~6–8 days)
  • Preservation of pulsatile GH secretion: pulse frequency and amplitude are unchanged while trough GH rises ~7.5-fold and mean 12-h GH rises ~46% (Ionescu & Frohman 2006)

Research Applications

CJC-1295 has been studied in two published Phase 1 trials in healthy adults, in several preclinical papers, and in one terminated Phase 2 trial (NCT00267527). The evidence base is small and largely from the ConjuChem programme of 2005–2009. All findings are reported as investigational and for research use only.

Identification and pharmacokinetics (preclinical, rat; Jetté 2005)

preclinical

Studies report that the CJC-1295–albumin conjugate produced a 4-fold increase in GH AUC over 2 hours versus unmodified hGRF(1-29) in cultured rat pituitary cells; CJC-1295 immunoreactivity in rat plasma was albumin-bound by 15 minutes and remained detectable beyond 72 hours. Identified CJC-1295 as the long-lasting GRF analogue lead.

— Jetté et al., Endocrinology 2005;146(7):3052–3058 (PMID 15817669)

Phase 1 ascending-dose study in healthy adults (Teichman 2006)

Phase I

Studies report dose-dependent increases of mean plasma GH of 2- to 10-fold for ≥6 days and IGF-1 of 1.5- to 3-fold for 9–11 days after single subcutaneous CJC-1295 with DAC at 30, 60, 90, 125, or 250 µg/kg; with multiple doses, IGF-1 remained above baseline for up to 28 days. Estimated terminal half-life 5.8–8.1 days; tolerability best at 30 and 60 µg/kg.

— Teichman et al., J Clin Endocrinol Metab 2006;91(3):799–805 (PMID 16352683)

Preserved GH pulsatility under continuous stimulation (Ionescu & Frohman 2006)

Phase I

Studies report unchanged GH pulse frequency and amplitude one week after a single 60- or 90-µg/kg subcutaneous CJC-1295 with DAC injection; trough GH rose ~7.5-fold, mean 12-h GH rose 46%, and IGF-1 rose 45%. Demonstrated that long-acting GHRH-receptor stimulation does not abolish physiological GH pulsatility.

— Ionescu & Frohman, J Clin Endocrinol Metab 2006;91(12):4792–4797 (PMID 17018654)

Restoration of normal growth in GHRH-knockout mice (Alba 2006)

preclinical

Studies report that GHRH-knockout mice receiving once-daily subcutaneous CJC-1295 with DAC at 2 µg for 5 weeks reached body length and weight indistinguishable from wild-type littermates; 48-h dosing partially normalised growth; 72-h dosing was insufficient. Established once-daily as the minimum-frequency regimen for full growth normalisation in this model.

— Alba et al., Am J Physiol Endocrinol Metab 2006;291(6):E1290–E1294 (PMID 16822960)

HIV-associated visceral adiposity (Phase 2, terminated; NCT00267527)

Phase II

Planned n=192, once-weekly CJC-1295 with DAC for up to 12 weeks vs placebo. Trial terminated by the sponsor on 17 July 2006 following the death of a participant at an Argentinian study site; the on-site investigator attributed the death to asymptomatic coronary artery disease with plaque rupture and occlusion rather than to study drug. No efficacy results were published; ConjuChem subsequently suspended the CJC-1295 programme in 2007–2008.

— ClinicalTrials.gov NCT00267527 (verified vs v2 API on 2026-05-01); aidsmap, 18 July 2006

Serum-protein biomarker analysis (Sackmann-Sala 2009)

Phase I

Studies report reproducible CJC-1295-induced changes in five serum proteins (apolipoprotein A1 isoform ↓, transthyretin isoform ↓, β-haemoglobin ↑, C-terminal albumin fragments ↑, immunoglobulin fragments ↑) with a linear correlation between albumin/Ig-fragment spot intensity and IGF-1.

— Sackmann-Sala et al., Growth Horm IGF Res 2009;19(6):471–477 (PMID 19386527)

Anti-doping detectability (Henninge 2010)

observational

Studies report unambiguous LC-MS/MS identification of CJC-1295 in a seized injectable preparation; demonstrated detectability of GHRH analogues in confiscated material and underpins the WADA listing of GHRH analogues under category S2.

— Henninge et al., Drug Test Anal 2010;2(11-12):647–650

Clinical Status

Regulatory Status
NOT approved by the FDA, EMA, Health Canada, or any other major regulatory agency. CJC-1295 has never reached marketing authorisation in any jurisdiction. Highest clinical phase: Phase 2 (NCT00267527, HIV-associated visceral obesity; terminated by the sponsor on 17 July 2006 following the death of a participant at an Argentinian study site — the on-site investigator attributed the death to asymptomatic coronary artery disease with plaque rupture and occlusion, not to study drug). The only confirmed CJC-1295 study on ClinicalTrials.gov is NCT00267527; verified against the ClinicalTrials.gov v2 API on 2026-05-01. Sport: prohibited by the World Anti-Doping Agency under category S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics), section S2.2.4 GH-releasing factors, in the 2026 Prohibited List — both in- and out-of-competition. Material from research-chemical suppliers is not regulatory approval and not a Triscience endorsement.
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Highest Trial Phase
Phase II (NCT00267527, terminated); other clinical data Phase I (healthy adults)
Sponsor
ConjuChem Inc. / ConjuChem Biotechnologies, Montréal, Canada (originator; lead candidate disclosed 2005, programme suspended 2007–2008)

Key Clinical Trials

  • A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study to Evaluate CJC-1295 in HIV-Infected Patients With HIV-Associated Visceral Obesity (ConjuChem GH100-013) — terminated 17 July 2006 after a participant death attributed by the site investigator to coronary artery disease; verified vs ClinicalTrials.gov v2 API on 2026-05-01.
    Phase 2
    NCT00267527

Safety Profile

Observed in research settings

In the published Phase 1 trials in healthy adults, CJC-1295 with DAC at 30 and 60 µg/kg was reported as well tolerated in research settings, with no serious adverse events attributed to study drug (Teichman 2006; Ionescu & Frohman 2006). The Phase 2 NCT00267527 trial was terminated after a single participant death; the on-site investigator attributed the death to underlying coronary disease, not to study drug — but the event prompted ConjuChem to suspend the programme (aidsmap 2006).

Adverse Events Reported in Studies

  • Injection-site reactions (pain, redness)
  • Transient facial flushing
  • Headache
  • Mild-to-moderate gastrointestinal symptoms (nausea) at higher doses (125–250 µg/kg)

Serious Adverse Events

  • One participant death in NCT00267527 (Phase 2, HIV-associated visceral obesity, Argentinian site, July 2006); attributed by the on-site investigator to asymptomatic coronary artery disease with plaque rupture and occlusion, not to study drug — but the trial was terminated and the broader programme subsequently suspended
  • Sustained IGF-1 elevation has been epidemiologically associated with risk signals across the GH/IGF-1 axis (e.g. neoplasia, insulin resistance); specific long-term safety data for CJC-1295 in any population are absent
  • Anti-doping liability: CJC-1295 is prohibited in sport under WADA category S2.2.4 (in- and out-of-competition) — documented detection methods exist (Henninge et al. 2010)

References

  1. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology 2005;146(7):3052–3058. 2005 .

    DOI: 10.1210/en.2004-1286 PMID: 15817669 View Source

  2. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne J-P, Frohman LA 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 2006;91(3):799–805. 2006 .

    DOI: 10.1210/jc.2005-1536 PMID: 16352683 View Source

  3. Ionescu M, Frohman LA Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab 2006;91(12):4792–4797. 2006 .

    DOI: 10.1210/jc.2006-1702 PMID: 17018654 View Source

  4. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne J-P, Frohman LA, Salvatori R 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 2006;291(6):E1290–E1294. 2006 .

    DOI: 10.1152/ajpendo.00201.2006 PMID: 16822960 View Source

  5. Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Horm IGF Res 2009;19(6):471–477. 2009 .

    DOI: 10.1016/j.ghir.2009.03.001 PMID: 19386527 View Source

  6. Henninge J, Pepaj M, Hullstein I, Hemmersbach P Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Test Anal 2010;2(11-12):647–650. 2010 .

    DOI: 10.1002/dta.233 View Source

  7. ConjuChem Inc. / ClinicalTrials.gov A Multicenter, Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study to Evaluate the Efficacy and Safety of CJC-1295 Administered for 12 Weeks in HIV Infected Patients With HIV-Associated Visceral Obesity (GH100-013). NCT00267527; verified vs ClinicalTrials.gov v2 API on 2026-05-01. ClinicalTrials.gov registry record. 2006 .

    View Source

  8. World Anti-Doping Agency The 2026 Prohibited List — International Standard. Section S2.2.4 (GH-releasing factors). WADA, effective 1 January 2026. 2026 .

    View Source

  9. PubChem CJC-1295 with DAC, CID 91971820 — molecular formula C₁₆₅H₂₆₉N₄₇O₄₆; CJC-1295 without DAC / Modified GRF 1-29, CID 91976842 — molecular formula C₁₅₂H₂₅₂N₄₄O₄₂. National Library of Medicine, PubChem records. 2025 .

    View Source

Frequently Asked Questions

What is CJC-1295?
CJC-1295 is a synthetic, tetra-substituted analogue of human growth-hormone-releasing hormone GHRH(1-29) developed by the Canadian biotechnology company ConjuChem. The four substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) make the peptide resistant to plasma DPP-IV cleavage. The lead with-DAC form additionally carries a Lys³⁰ maleimidopropionyl group that covalently binds the free thiol on Cys³⁴ of serum albumin in vivo, extending its plasma half-life from minutes (sermorelin) to roughly 6–8 days.
What is the difference between CJC-1295 with DAC and CJC-1295 without DAC?
They are two chemically distinct entities that share the same tetra-substituted GHRH(1-29) backbone but differ at the C-terminus. With DAC carries an extra Lys³⁰ residue bearing an Nε-maleimidopropionyl group (formula C₁₆₅H₂₆₉N₄₇O₄₆, MW ≈ 3647 Da, half-life ~6–8 days). Without DAC (also called Modified GRF 1-29) lacks that extension (formula C₁₅₂H₂₅₂N₄₄O₄₂, MW ≈ 3368 Da, half-life ~30 minutes). ConjuChem advanced the with-DAC form into clinical trials; the without-DAC form is what is most often encountered in research-chemical supply.
How does CJC-1295 differ from sermorelin and tesamorelin?
All three engage the GHRH receptor, but their pharmacokinetic profiles differ by orders of magnitude. Sermorelin is unmodified GHRH(1-29) (t½ ≈ 11–12 min); CJC-1295 without DAC adds DPP-IV-resistance substitutions (t½ ≈ 30 min); tesamorelin is GHRH(1-44) with N-terminal trans-3-hexenoyl protection (t½ ≈ 26 min); and CJC-1295 with DAC binds covalently to albumin for a t½ of ~6–8 days. Of these, only tesamorelin has FDA approval (for HIV-associated lipodystrophy); sermorelin's US approval was voluntarily discontinued in 2008; CJC-1295 has never been approved.
Is CJC-1295 approved by the FDA or EMA?
No. CJC-1295 is NOT approved by the FDA, EMA, Health Canada, or any other major regulator. ConjuChem's clinical programme reached Phase 2 (NCT00267527, HIV-associated visceral obesity) but was terminated in July 2006 after the death of a study participant; the on-site investigator attributed the death to underlying coronary disease rather than to study drug. Material currently in circulation is from research-chemical suppliers, which is not the same as regulatory approval.
What does the published clinical PK/PD literature show?
Across two Phase 1 studies in healthy adults, single subcutaneous CJC-1295 with DAC produced dose-dependent rises of mean GH (2- to 10-fold for ≥6 days) and IGF-1 (1.5- to 3-fold for 9–11 days), with multi-dose IGF-1 elevation persisting up to 28 days and an estimated terminal half-life of 5.8–8.1 days (Teichman 2006). A second study showed that GH pulsatility was preserved even under continuous receptor stimulation: pulse frequency and amplitude were unchanged while trough GH rose ~7.5-fold (Ionescu & Frohman 2006).
Is CJC-1295 banned in sport?
Yes. CJC-1295 is prohibited under the World Anti-Doping Agency (WADA) Prohibited List, category S2 (Peptide Hormones, Growth Factors, Related Substances and Mimetics), section S2.2.4 (GH-releasing factors), in the 2026 list — applicable both in- and out-of-competition. Detection methods for GHRH analogues including CJC-1295 are published (Henninge et al., Drug Test Anal 2010).

Related Peptides

Sermorelin

≥98%

GHRH(1-29) Receptor Agonist (Growth-Hormone Secretagogue, GRF Class)

Synthetic GHRH(1-29) amide (Geref); the shortest fragment of human growth-hormone-releasing hormone that retains full biological activity — historically FDA-approved for pediatric GH deficiency and voluntarily withdrawn from the US market in 2008 for commercial reasons.

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Tesamorelin

≥98%

GHRH(1-44) Receptor Agonist (Growth-Hormone Secretagogue, GRF Class)

Stabilised synthetic GHRH(1-44) analogue (TH9507) developed by Theratechnologies and FDA-approved as Egrifta, Egrifta SV, and Egrifta WR for the reduction of excess visceral abdominal fat in HIV-associated lipodystrophy; not authorised in the European Union.

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Ipamorelin

≥98%

Pentapeptide GHSR-1a Agonist (Ghrelin Mimetic, GHRP Class)

Synthetic pentapeptide and selective GHSR-1a agonist (ghrelin receptor) developed by Novo Nordisk (NNC 26-0161). Notable for the historically cleanest selectivity within the GHRP class: GH release without measurable ACTH, cortisol, prolactin, FSH, LH or TSH elevation. NOT approved; Phase 2 program failed.

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