What CJC-1295 is

CJC-1295 is a synthetic 30-amino-acid analog of growth hormone–releasing hormone (GHRH) developed in the early 2000s by ConjuChem, in which key residues of native GHRH(1–29) are substituted (D-Ala²-Gln⁸-Ala¹⁵-Leu²⁷) to increase metabolic stability. Two variants are referenced in the literature: a non-DAC form (often called modified GRF 1-29 or CJC-1295 without DAC) with a half-life of approximately 30 minutes, and a Drug Affinity Complex (DAC) form bearing a maleimidopropionic-acid linker that covalently binds circulating albumin, extending serum half-life to approximately one to two weeks in humans (Teichman et al., 2006 — PMID 16352683). The compound is studied in models of pituitary GH secretion and the GHRH-receptor signaling axis.

Mechanism of action

CJC-1295 binds the GHRH receptor (GHRHR), a class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs. Receptor activation engages Gαs, increasing intracellular cyclic AMP and activating protein kinase A, which leads to phosphorylation of CREB and transcription of the GH gene, as well as exocytosis of pre-formed GH secretory granules. Unlike short-acting GHRH analogs, the DAC-bearing variant maintains continuous low-level GHRHR engagement; published pharmacodynamic work indicates that despite continuous albumin-bound exposure, GH secretion remains pulsatile because pulsatility is driven primarily by hypothalamic somatostatin withdrawal (Teichman et al., 2006 — PMID 16352683). Sustained GHRHR signaling elevates mean GH and IGF-1 concentrations without abolishing physiologic pulsing.

Historical & structural context

Native GHRH(1–44) was isolated and sequenced in 1982 from pancreatic tumors causing acromegaly, with subsequent demonstration that the bioactive core resides in residues 1–29. Several short-acting GHRH(1–29) analogs were developed in the 1980s and 1990s — including sermorelin and modified GRF(1–29) — but their utility was constrained by rapid DPP-IV cleavage and renal clearance. CJC-1295 represents a third-generation approach that combines stabilizing residue substitutions with maleimidopropionic-acid (MPA) Drug Affinity Complex chemistry, a covalent albumin-conjugation strategy applicable to many bioactive peptides. The MPA linker forms a Michael-addition adduct with the free thiol of cysteine-34 of circulating human serum albumin, dramatically extending half-life.

Methodological considerations

Researchers designing CJC-1295 protocols should account for (1) potential differences between non-DAC and DAC variants in pharmacokinetics, target engagement duration, and pulsatility preservation; (2) variability in serum albumin concentration across animal models and disease states, which directly affects DAC-form distribution; (3) the contribution of endogenous somatostatin tone to apparent GH-axis responsiveness, which can mask receptor-level pharmacology; (4) appropriate IGF-1 sampling intervals, which should be informed by the multi-day half-life of the DAC variant rather than the 30-minute half-life of the non-DAC variant.

Research applications

CJC-1295 is used in non-clinical and clinical pharmacology research to:

Map GHRHR pharmacokinetics and the contribution of albumin-binding extension chemistry to peptide half-life (Jetté et al., 2005 — PMID 15817669).
Probe GH/IGF-1 axis dynamics in healthy adult cohorts (Teichman et al., 2006 — PMID 16352683).
Examine pulsatile secretion patterns when GHRH input is held continuously elevated.
Provide a reference long-acting GHRH agonist for comparison against secretagogue receptor (GHS-R) agonists such as ipamorelin.
Investigate albumin-conjugation as a generalized peptide half-life extension strategy.

Stability & handling notes

Lyophilized CJC-1295 is typically stable at −20 °C for up to 24 months. Reconstituted solutions are aliquoted to minimize freeze–thaw cycles. The DAC variant is sensitive to free thiols and to prolonged exposure to plasma esterases in solution; storage of working solutions at 2–8 °C beyond 14 days is generally not recommended.

Common research dosing reference

Published Phase I human pharmacology reported single subcutaneous doses of 30, 60, and 250 μg/kg for the DAC variant, with sustained IGF-1 elevation observed for 6–8 days at the higher doses (Teichman et al., 2006). These figures are research benchmarks only and have no implication for clinical dosing or therapeutic application.

Quality & specifications

Reference-grade material is typically characterized by reverse-phase HPLC purity ≥98%, electrospray-ionization mass spectrometry (ESI-MS) confirming the expected monoisotopic mass, and quantitative amino-acid analysis where applicable. Cell-culture-grade lots additionally include endotoxin testing by Limulus amebocyte lysate (LAL) assay and bioburden screening. Each lot is shipped with a Certificate of Analysis itemizing purity, identity, residual solvents, water content (Karl Fischer), and acetate or trifluoroacetate counter-ion content where relevant. Investigators evaluating new lots should request raw chromatograms and mass spectra prior to incorporation into published work.

Pharmacology in context

CJC-1295 belongs to a series of GHRH analogs that have been progressively engineered for improved pharmacokinetics: native GHRH(1–44) and GHRH(1–29) are short-acting; sermorelin (GHRH(1–29)NH₂) extends serum exposure modestly; modified GRF(1–29) introduces residue substitutions for protease resistance; tesamorelin uses N-terminal acylation to block DPP-IV; and CJC-1295 with DAC adds covalent albumin conjugation for week-scale exposure. Each analog occupies a distinct niche for mechanistic and translational research. Comparative work that titrates these analogs against ipamorelin, hexarelin, or anamorelin has substantially advanced understanding of how GHRH and GHS-R signaling integrate at the somatotroph level.

Reporting & reproducibility expectations

Publications using CJC-1295 should clearly state: (a) DAC versus non-DAC variant, since the two have distinct pharmacokinetics and should not be conflated; (b) supplier, lot, HPLC purity, and mass-spec verification; (c) reconstitution buffer and storage history, with attention to thiol contamination given the maleimide chemistry of the DAC variant; (d) dosing route, frequency, and total exposure; (e) for IGF-1 readouts, sampling timepoints chosen to capture the appropriate kinetic window; (f) baseline GH and IGF-1 values for all subjects, since substantial inter-individual variability is expected. Lot-to-lot consistency of DAC chemistry should be confirmed by mass spectrometry showing the expected albumin adduct.

Compliance & regulatory framing

This material is provided strictly for research and educational reference. The compound is supplied for in vitro investigation and laboratory characterization only and is not intended for human ingestion, injection, topical use, or any clinical application. Federal and state law treats research peptides as non-therapeutic chemicals; recipients are responsible for compliance with all applicable institutional, state, and federal regulations governing handling, storage, and disposal. Pricing, availability, and supply specifications are subject to change without notice. Request a Certificate of Analysis (COA), HPLC chromatograms, mass-spec verification, or compliance documentation from the Clinical Advisory Team for any specific lot.

Related research compounds

Researchers studying the GH axis often co-reference Ipamorelin as a complementary GHS-R agonist, the dual CJC-1295 + Ipamorelin 10 mg blend, and Tesamorelin 15 mg as another GHRH analog with documented clinical pharmacology.

Sourcing & analytical verification

For DAC variant lots, mass-spec verification should confirm both the expected mass of the modified peptide and, ideally, the formation of the maleimide-albumin adduct under defined conditions. Investigators should request lot-specific HPLC chromatograms and any available stability data. Endotoxin testing is required for any cell-culture or in vivo work, since pituitary somatotrophs are responsive to inflammatory stimuli that can confound GH-axis pharmacology readouts. Orthogonal verification of pharmacodynamic activity in a reference assay (e.g. GH release from cultured pituitary cells) provides additional confidence beyond chemical characterization alone, particularly for DAC chemistry where minor batch variations can substantially affect albumin-binding kinetics and apparent half-life.

References

References below are anchor PubMed citations. Readers are encouraged to verify each in the National Library of Medicine database before using as a research source.

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CJC-1295 – GHRH Analog Research Summary