What Is CJC-1295?
CJC-1295 is a synthetic analogue of growth hormone-releasing hormone (GHRH) — the hypothalamic peptide that stimulates pituitary somatotrophs to synthesise and secrete growth hormone (GH). It exists in two distinct research forms that differ fundamentally in their pharmacokinetic profiles: CJC-1295 without DAC (also known as MOD GRF 1-29 or Modified GRF(1-29)) and CJC-1295 with DAC (Drug Affinity Complex). Understanding the mechanistic and pharmacokinetic distinction between these two variants is central to any rigorous study of the GH secretion axis.
This guide covers the molecular biology of both CJC-1295 variants, their mechanisms of action at the GHRH receptor, the pharmacokinetic implications of the DAC modification, key research applications, and their positioning within the broader landscape of GH-axis research compounds.
Molecular Structure and Properties
Both CJC-1295 variants share a common structural foundation — a 29-amino acid sequence corresponding to the biologically active N-terminal fragment of native human GHRH (hGHRH(1-29)NH₂), with four key amino acid substitutions that improve metabolic stability:
- Position 2: Alanine → D-Alanine (resistance to dipeptidyl peptidase IV cleavage)
- Position 8: Asparagine → Glutamine (reduced deamidation)
- Position 15: Glycine → Alanine (improved conformational stability)
- Position 27: Methionine → Norleucine (oxidation resistance)
These substitutions collectively extend the metabolic half-life of the native GHRH(1-29) fragment from under two minutes to approximately 30 minutes in the No DAC form.
CJC-1295 No DAC (MOD GRF 1-29):
- Molecular weight: ~3,367 Da
- Half-life: ~30 minutes
- Amino acids: 29
- Receptor target: GHRH receptor (GHRHR) on anterior pituitary somatotrophs
- Supplied as: lyophilised powder for in vitro research use
CJC-1295 with DAC:
- Molecular weight: ~3,647 Da (with maleimide-lysine conjugate)
- Half-life: 6–8 days (via reversible albumin binding)
- Modification: Lys²⁰ maleimide-DAC conjugate enabling covalent albumin binding
- Receptor target: GHRHR (same primary target; albumin serves as a depot carrier)
- Supplied as: lyophilised powder for in vitro and preclinical research use
Mechanism of Action: GHRHR Agonism
Both CJC-1295 variants act as agonists at the growth hormone-releasing hormone receptor (GHRHR) — a Gs-protein-coupled receptor (GPCR) expressed predominantly on anterior pituitary somatotrophs. The receptor activation cascade is shared between both variants and proceeds as follows:
- Gs coupling: GHRHR engagement activates the Gs alpha subunit, stimulating adenylyl cyclase and raising intracellular cyclic AMP (cAMP)
- PKA activation: Elevated cAMP activates protein kinase A, which phosphorylates CREB (cAMP response element-binding protein)
- GH gene transcription: Phosphorylated CREB drives transcription of the GH1 gene, increasing cellular GH synthesis — a mechanism distinct from GHSR-1a agonists such as Ipamorelin, which primarily stimulate GH secretion without directly upregulating GH gene expression
- GH secretion: PKA-mediated signalling promotes GH secretory granule exocytosis; cAMP also activates L-type voltage-gated calcium channels, augmenting calcium-dependent vesicular release
This dual effect on GH synthesis and secretion — operating through a distinctly different receptor pathway to GHSR-1a agonists — is the primary reason CJC-1295 is used in combination with Ipamorelin in GH axis research models.
DAC vs No DAC: Pharmacokinetic Comparison
The DAC (Drug Affinity Complex) modification is the defining pharmacokinetic feature that separates the two CJC-1295 research variants. Understanding this distinction is essential for selecting the appropriate compound for a given research model.
The DAC Mechanism
The DAC modification adds a maleimide group at lysine position 20. Once administered, this maleimide reacts with free thiol groups on circulating serum albumin — the most abundant plasma protein (half-life: ~19 days) — forming a stable but slowly reversible covalent bond. Albumin acts as a high-capacity endogenous depot, releasing CJC-1295 gradually to maintain sustained GHRHR stimulation.
Teichman et al. (2006, Journal of Clinical Endocrinology and Metabolism) characterised the pharmacokinetics of CJC-1295 with DAC in healthy adult volunteers, reporting a mean half-life of 5.8–8.1 days and sustained, dose-dependent elevations in plasma GH and IGF-1 lasting up to 14 days following a single injection. This study remains the primary pharmacokinetic reference for CJC-1295 DAC.
| Property | CJC-1295 No DAC (MOD GRF 1-29) | CJC-1295 with DAC |
|---|---|---|
| Half-life | ~30 minutes | 6–8 days |
| GH release pattern | Pulsatile (physiological) | Sustained / continuous elevation |
| Albumin binding | None | Reversible covalent binding via maleimide-DAC |
| Receptor occupancy | Transient | Prolonged, depot-driven |
| Research utility | Pulsatile GH models, somatotroph pharmacology, combination stacks | Sustained GH elevation models, long-duration IGF-1 studies |
| Somatostatin feedback risk | Lower (pulsatile profile largely bypasses tonic somatostatin) | Higher with continuous elevation |
Research Implications of the Pulsatile vs. Continuous Distinction
GH is physiologically secreted in discrete pulses — primarily nocturnal — driven by the coordinated interplay of hypothalamic GHRH stimulation and somatostatin (SRIF) inhibition. Continuous GH elevation, as achieved with CJC-1295 DAC, produces a different downstream metabolic and receptor-level response than pulsatile GH release. Research groups studying somatotroph desensitisation, GH receptor downregulation, or the differential effects of GH pulse amplitude versus frequency should select CJC-1295 No DAC for its physiologically congruent profile.
Research Applications
GH Axis Pharmacology
CJC-1295 (both variants) is a primary tool compound for GHRHR receptor pharmacology studies. Its improved metabolic stability over native GHRH(1-29) makes it suitable for in vitro receptor binding assays, cAMP accumulation studies, and pituitary cell culture models examining somatotroph signal transduction. The No DAC variant’s defined ~30-minute action window enables controlled pulsatile stimulation paradigms.
IGF-1 Axis Research
GH released in response to GHRHR agonism drives hepatic IGF-1 synthesis via JAK2/STAT5b signalling. CJC-1295 with DAC’s prolonged GH elevation profile has been used in preclinical models to study sustained IGF-1 axis activation, hepatic GH receptor responsiveness, and the downstream anabolic and metabolic effects of chronic IGF-1 elevation. Teichman et al. (2006) reported mean IGF-1 increases of 50–100% persisting for up to two weeks following CJC-1295 DAC administration.
Body Composition and Metabolic Models
GH exerts direct lipolytic effects through hormone-sensitive lipase activation and indirect anabolic effects via IGF-1. Preclinical models have employed GHRH analogues — including CJC-1295 — to examine GH-mediated changes in adipose tissue, lean mass accrual, and glucose homeostasis. These studies are conducted strictly within in vitro and animal model frameworks.
Somatotroph Biology and Feedback Regulation
CJC-1295 No DAC is used in studies examining hypothalamic-pituitary feedback, including the role of somatostatin in attenuating GHRH-driven GH release, GH autofeedback via short-loop mechanisms, and pituitary somatotroph responsiveness under various physiological states (e.g., fasting, ageing models).
Ageing and Somatopause Research
Age-related decline in GH secretion — somatopause — is characterised by reduced GHRH signalling, increased somatostatin tone, and diminished pituitary somatotroph responsiveness. GHRH analogues, including CJC-1295, have been used in aged animal models to investigate whether restoration of GHRHR stimulation can partially reverse somatopause-associated declines in IGF-1 and body composition. Alba et al. (2006, American Journal of Physiology — Endocrinology and Metabolism) demonstrated sustained GH axis stimulation in a rodent model using a long-acting GHRH analogue, providing a preclinical framework for this research area.
CJC-1295 vs Related GH-Axis Research Compounds
CJC-1295 sits within a broader family of GH-axis research peptides. Understanding its mechanistic position relative to comparators is essential for research design:
CJC-1295 vs Sermorelin
Sermorelin is an earlier synthetic GHRH analogue — the native hGHRH(1-29)NH₂ sequence without the four stabilising amino acid substitutions present in CJC-1295. Its half-life is substantially shorter (minutes vs. ~30 minutes for CJC-1295 No DAC), making it a less practical tool compound for most research models. CJC-1295 No DAC is considered the improved successor for controlled GHRHR agonism research.
CJC-1295 vs Ipamorelin (GHSR-1a vs GHRHR)
Ipamorelin is a selective GHSR-1a (growth hormone secretagogue receptor 1a) agonist — it acts at an entirely different receptor to CJC-1295. Where CJC-1295 activates the GHRHR/cAMP/PKA/CREB pathway to drive GH synthesis and secretion, Ipamorelin mimics ghrelin at GHSR-1a, stimulating GH release primarily through calcium-dependent secretory mechanisms without directly upregulating GH gene transcription. For a detailed profile of Ipamorelin’s mechanism and research applications, see: Ipamorelin: Mechanism of Action and Growth Hormone Research Overview.
CJC-1295 vs GHRP Peptides (GHRP-2, GHRP-6)
GHRP-2 and GHRP-6 are growth hormone-releasing peptides that, like Ipamorelin, act at GHSR-1a. Unlike Ipamorelin, they are less selective — GHRP-6 in particular stimulates significant ghrelin-mediated appetite signalling, and GHRP-2 has measurable effects on prolactin and cortisol in some models. CJC-1295’s GHRHR agonism is mechanistically independent of this receptor class, making it complementary rather than competitive in dual-pathway GH research designs.
Research Stacks: CJC-1295 and Ipamorelin
The combination of a GHRHR agonist (CJC-1295 No DAC) with a GHSR-1a agonist (Ipamorelin) is one of the most widely employed dual-pathway approaches in GH axis research. The mechanistic rationale reflects fundamental GH physiology: in vivo, GH secretion is co-regulated by hypothalamic GHRH (via GHRHR) and ghrelin/synthetic GHS (via GHSR-1a), and dual receptor stimulation produces synergistic GH release that substantially exceeds either compound alone.
This synergistic interaction has been characterised in preclinical models and underpins the design of combination research preparations. Petersenn et al. (2000, Endocrinology) demonstrated that co-administration of GHRH and GHSR agonists produced additive to synergistic GH responses in rodent pituitary cell preparations, consistent with converging but mechanistically distinct intracellular signalling cascades — cAMP/PKA (GHRHR) and phospholipase C/IP₃/Ca²⁺ (GHSR-1a).
For researchers requiring both pathways in a single preparation, R&D Peptides supplies a CJC-1295 No DAC / Ipamorelin Combination Pen, supplied with a batch-specific Certificate of Analysis for in vitro research use.
Researchers also have the option of sourcing each compound individually: CJC-1295 No DAC 10mg and Ipamorelin 10mg, allowing independent dosing protocols.
Research Status and Literature
CJC-1295 has a well-characterised pharmacokinetic and pharmacodynamic profile documented across peer-reviewed literature:
- Teichman et al. (2006), Journal of Clinical Endocrinology and Metabolism: Characterised the pharmacokinetics of CJC-1295 with DAC in healthy adults; reported half-life of 5.8–8.1 days, sustained GH and IGF-1 elevation, and a favourable tolerability profile at doses of 30–120 mcg/kg
- Alba et al. (2006), American Journal of Physiology — Endocrinology and Metabolism: Demonstrated that long-acting GHRH analogue administration in aged rats restored GH pulse amplitude and IGF-1 levels toward those of young controls, supporting the utility of GHRH analogues in somatopause models
- Ionescu and Frohman (2006), Journal of Clinical Endocrinology and Metabolism: Reviewed GHRH analogue pharmacology, including the structural and pharmacokinetic rationale for extended-half-life modifications such as DAC conjugation
- Walker et al. (2021), Peptides: Examined GHRH receptor signalling and the role of pulsatile versus continuous GHRH stimulation in somatotroph responsiveness and GH axis homeostasis
CJC-1295 (both variants) is not approved for human administration. It is available exclusively as an in vitro research compound and is not a licensed pharmaceutical.
Sourcing CJC-1295 for Research
R&D Peptides supplies CJC-1295 No DAC in two formats for research applications:
- CJC-1295 No DAC 10mg Research Pen — lyophilised, with batch-specific Certificate of Analysis
- Ipamorelin 10mg / CJC-1295 No DAC 5mg Combination Pen — dual-pathway preparation for GH axis research
All products are supplied strictly for in vitro research use only, accompanied by third-party verified Certificates of Analysis. For quality and testing standards, see our quality and testing page, or review our guidance on interpreting Certificates of Analysis for peptide research.
For mechanistic context on the No DAC variant specifically, see: CJC-1295 No DAC (MOD GRF 1-29): Mechanism of Action and GH Research.
All content on this page is for educational and informational purposes only. CJC-1295 is supplied by R&D Peptides strictly for in vitro research use. It is not intended for human or veterinary administration, and no therapeutic claims are made or implied.
