Secretagogue
A long-acting, albumin-binding GHRH (GRF 1-29) analog studied as a research tool for the growth-hormone / IGF-1 neuroendocrine axis and class B GPCR pharmacology.
CJC-1295 with DAC is a synthetic, chemically modified fragment of growth-hormone-releasing hormone (the first 29 amino acids of GRF) that carries a Drug Affinity Complex (DAC) — a maleimidopropionyl-lysine group that binds covalently to circulating serum albumin. It is studied in endocrine pharmacology as a tool for examining engagement of the GHRH receptor, a class B GPCR on pituitary somatotrophs, and the GH / insulin-like growth factor-1 (IGF-1) signaling axis. It shares its peptide backbone with a shorter-circulating non-DAC variant (Modified GRF 1-29). It is supplied for research use only and is not for human or veterinary use.
Type
Synthetic peptide (tetrasubstituted GRF(1-29) analogue with an albumin-binding DAC group)
Molecular formula
C165H269N47O46
Molecular weight
~3,647 g/mol
CAS number
863288-34-0
Amino acids
30
Sequence
H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys-NH2 (Nε-3-maleimidopropionyl on the C-terminal Lys30)
Modification
Four substitutions relative to GRF(1-29) — D-Ala2, Gln8, Ala15, Leu27 — conferring resistance to dipeptidyl peptidase-4 and other plasma proteases; C-terminal amidation; and an Nε-3-maleimidopropionyl-Lys30 (DAC) linker whose maleimide forms a covalent thioether bond with cysteine-34 of serum albumin.
A synthetic analogue of growth-hormone-releasing hormone (GRF 1-29) that acts as an agonist at the GHRH receptor (GHRHR), a class B / secretin-family G-protein-coupled receptor on anterior-pituitary somatotrophs. Like other class B GPCRs, GHRHR is Gs-coupled and engages the adenylyl-cyclase / cAMP / PKA pathway; structurally it comprises an extracellular domain and a seven-transmembrane bundle bound by the peptide via the canonical two-domain mechanism. Two structural features distinguish the molecule: a tetrasubstituted GRF(1-29) backbone (D-Ala2, Gln8, Ala15, Leu27) that resists protease cleavage, and a Drug Affinity Complex — an Nε-maleimidopropionyl-lysine appended at the C-terminus whose maleimide reacts with the free thiol on cysteine-34 of serum albumin, converting the peptide into a long-circulating albumin conjugate.
Research Focus
Studied in GHRH-receptor pharmacology, peptide pharmacokinetics and albumin-conjugation chemistry, structural GPCR biology, and analytical detection methods.
CJC-1295 with DAC was first characterized in the peer-reviewed literature by Jetté and colleagues (2005) in Endocrinology. That work synthesized maleimido derivatives of human GRF(1-29) and bioconjugated them to serum albumin, exploiting the free thiol on cysteine-34 of albumin as a general strategy to extend a peptide's plasma half-life. The underlying Drug Affinity Complex (DAC) platform is a three-part design — a bioactive peptide, a linker, and a thiol-selective maleimide group. The selected lead was a tetrasubstituted form of GRF(1-29) carrying an Nε-3-maleimidopropionamide derivative of lysine at the C-terminus. The study examined in-vitro dipeptidyl peptidase-4 stability and GH-secretion bioactivity in cultured rat anterior-pituitary cells, together with acute GH responses in rats, and tracked the appearance of an albumin-comigrating immunoreactive species in circulation.
At the receptor level, the literature places CJC-1295 within GHRH-receptor pharmacology. The GHRHR is a class B GPCR, and the determinants of ligand recognition and activation for this receptor family have been examined by cryo-electron microscopy. Zhou and colleagues (2020) reported the cryo-EM structure of the human GHRHR bound to its native hormone and the stimulatory Gs protein, describing the hormone-recognition pattern, the role of the extracellular domain and loops, and the conserved class B activation mechanism (outward movement of transmembrane helix 6). That structural study examined the native hormone rather than CJC-1295 itself, but it provides the mechanistic framework for how GRF(1-29)-based analogues engage the receptor's two-domain binding site.
Human pharmacology was characterized by Teichman and colleagues (2006) in the Journal of Clinical Endocrinology & Metabolism: randomized, placebo-controlled, double-blind studies in adults that measured peak concentrations, area-under-the-curve, and standard pharmacokinetic parameters of GH and IGF-1 following single and repeated administration. A companion study by Ionescu and Frohman (2006), also in JCEM, applied GH-pulsatility (deconvolution) analysis to determine which GH-secretion parameters correlated with the IGF-1 measurement during sustained GHRH-receptor stimulation, and examined whether pulsatile GH secretion persists under continuous stimulation. In a preclinical model, Alba and colleagues (2006) in the American Journal of Physiology-Endocrinology and Metabolism administered the compound to GHRH-knockout mice and measured skeletal growth parameters (body and bone length) and pituitary GH mRNA with somatotroph immunohistochemistry, comparing different study schedules; the paper noted that species-specific albumin half-life differs across species. A registered Phase 2 study (NCT00267527) examined CJC-1295 with DAC in a clinical research setting.
Sackmann-Sala and colleagues (2009) in Growth Hormone & IGF Research used CJC-1295 with DAC as a tool to identify candidate serum biomarkers associated with the GH/IGF-1 axis. Serum samples were albumin-depleted, separated by two-dimensional gel electrophoresis, and differentially abundant proteins were identified by MALDI-TOF and MALDI-TOF/TOF mass spectrometry; the study examined spots identified as apolipoprotein A1 and transthyretin isoforms, along with albumin and immunoglobulin fragments, and their correlation with the IGF-1 measurement.
A body of analytical-methods literature examines the detection and identification of CJC-1295. Henninge and colleagues (2010, Drug Testing and Analysis) characterized a CJC-1295-type 29-amino-acid C-terminally amidated peptide by LC-HRMS/MS. Knoop and colleagues (2016, Analytical and Bioanalytical Chemistry) developed and validated an immunoaffinity-purification LC-HRMS/MS assay for the simultaneous detection of multiple GHRH analogues (including CJC-1295) and their metabolites in human plasma, characterizing stability and biotransformation. Because the DAC conjugate behaves as a high-molecular-weight albumin adduct that evades top-down peptide screening, Timms and colleagues (2019, Drug Testing and Analysis) developed an immuno-polymerase-chain-reaction (immuno-PCR) assay for the albumin-conjugated form, validated in a plasma matrix. A later review by Memdouh and colleagues (2021) surveys advances in detecting GHRH synthetic analogues.
Lyophilized
-20°C
protected from light and moisture; frozen for longer-term storage.
Reconstituted
-20°C frozen for longer storage
2-8°C for short-term working use only.
As a peptide, susceptible to degradation from heat, light, moisture, and repeated freeze-thaw. The DAC maleimide group is thiol-reactive. Research-use-only; not for human or veterinary use.
Reviews
Memdouh S, et al. (2021). Drug Test Anal — Review of analytical methods for detecting GHRH synthetic analogues including CJC-1295 with DAC
Sinha DK, et al. (2020). Transl Androl Urol — Narrative review of growth-hormone-secretagogue pharmacology including the GHRH analogue CJC-1295 with DAC
Sigalos JT, Pastuszak AW. (2018). Sex Med Rev — Review of growth-hormone secretagogues (GHRH analogues and GH-releasing peptides) in human subjects
Clinical
Teichman SL, et al. (2006). J Clin Endocrinol Metab — Randomized pharmacokinetic and pharmacodynamic study measuring GH and IGF-1 parameters of CJC-1295 with DAC in adults
Ionescu M, Frohman LA. (2006). J Clin Endocrinol Metab — Human study applying GH-pulsatility (deconvolution) analysis during sustained GHRH-receptor stimulation by CJC-1295 with DAC
ClinicalTrials.gov registry. ClinicalTrials.gov — Registered Phase 2 clinical study of CJC-1295 with DAC (GH / IGF-1 axis research)
Primary research
Zhou F, et al. (2020). Nat Commun — Cryo-EM structural study of the human GHRH receptor (the target receptor of CJC-1295 with DAC) bound to GHRH and Gs
Timms M, et al. (2019). Drug Test Anal — Immuno-PCR analytical study detecting the albumin-conjugated form of CJC-1295 with DAC in a plasma matrix
Knoop A, et al. (2016). Anal Bioanal Chem — Validated immunoaffinity LC-HRMS/MS analytical study detecting GHRH analogues including CJC-1295 with DAC in human plasma
Henninge J, et al. (2010). Drug Test Anal — LC-HRMS/MS analytical identification of a CJC-1295-type GRF peptide
Sackmann-Sala L, et al. (2009). Growth Horm IGF Res — Serum-proteomics biomarker-discovery study (2D-PAGE / MALDI-TOF) of the GH/IGF-1 axis using CJC-1295 with DAC
Alba M, et al. (2006). Am J Physiol Endocrinol Metab — Preclinical study of CJC-1295 with DAC in the GHRH-knockout mouse measuring growth and pituitary GH-mRNA parameters
Jetté L, et al. (2005). Endocrinology — Lead-identification and preclinical characterization study of CJC-1295 with DAC (in-vitro GH-secretion assays, DPP-IV stability, rat pharmacokinetics)
Also known as: CJC-1295 DAC, Mod GRF 1-29 (non-DAC variant)
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
