CJC-1295 (no DAC) + Ipamorelin Blend Peptide

This research blend co-formulates two complementary growth-hormone secretagogues that act on distinct but converging signaling pathways within anterior pituitary somatotrophs: CJC-1295 without DAC (also known as Mod GRF 1-29 or tetra-substituted GRF 1-29), a stabilized analog of growth-hormone-releasing hormone (GHRH), and Ipamorelin, a selective pentapeptide agonist of the growth-hormone secretagogue receptor (GHS-R1a, the ghrelin receptor).

CJC-1295 (no DAC) is a 30-residue peptide derived from human GHRH(1-29) with four amino-acid substitutions — D-Ala² (DPP-IV resistance), Gln⁸ (reduced asparagine deamidation), Ala¹⁵ (enhanced bioactivity), and Leu²⁷ (oxidation resistance). These modifications extend the in vivo half-life of the parent GHRH(1-29) sequence from approximately 7 minutes to roughly 30 minutes while preserving full agonist activity at the GHRH receptor (GHRHR), a class B G-protein-coupled receptor. GHRHR activation stimulates Gαs-coupled adenylyl cyclase, elevating intracellular cAMP, activating protein kinase A, and triggering GH gene transcription and exocytotic GH release. Unlike the DAC-modified variant (CJC-1295 with DAC, which conjugates to serum albumin via a maleimidopropionic-acid linker for multi-day half-life), the non-DAC version provides a discrete, pulsatile signal that more closely mimics endogenous GHRH kinetics.

Ipamorelin (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) is a pentapeptide GHS-R1a agonist that activates the Gαq/phospholipase-C/IP₃ pathway in somatotrophs, mobilizing intracellular calcium and amplifying GH exocytosis. Crucially, ipamorelin demonstrates high selectivity for GHS-R1a with minimal stimulation of adrenocorticotropic hormone (ACTH), cortisol, or prolactin secretion at GH-releasing doses — a pharmacological profile that distinguishes it from earlier ghrelin mimetics such as GHRP-6 and GHRP-2 (Raun et al., 1998, PMID 9849822).

Mechanistic rationale for combining the two peptides:

• Pathway convergence: GHRH and ghrelin pathways activate independent G-protein cascades (Gαs/cAMP and Gαq/IP₃-Ca²⁺, respectively) that converge on GH exocytosis. Co-stimulation produces additive — and in several preclinical models, supra-additive — GH release compared to either agent alone.
• Somatostatin suppression: Ghrelin-receptor agonism also reduces hypothalamic somatostatin tone, removing the principal inhibitory brake on pituitary GH secretion and amplifying the GHRH signal.
• Pulsatile physiology: The short half-life of both peptides in this blend (no-DAC CJC-1295 ~30 min; ipamorelin ~2 h) generates discrete GH pulses rather than sustained elevation, preserving physiological feedback architecture.
• Selectivity: Ipamorelin's lack of cortisol/prolactin co-secretion provides a cleaner pharmacological readout for studies focused specifically on the somatotropic axis.

Research applications in published literature include investigation of GH/IGF-1 axis regulation, somatotroph signaling integration, secretagogue pharmacology, comparative dose-response studies versus monotherapy, and characterization of pulsatile versus tonic GH-release paradigms in animal and in vitro models.

Reference: Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. PMID 9849822

For laboratory research use only. Not for human or veterinary use, diagnosis, or treatment.

The CJC-1295/Ipamorelin combination activates two distinct receptor systems on pituitary somatotrophs simultaneously:

• CJC-1295 → GHRH Receptor (GHRH-R): Gs-coupled receptor activation → adenylyl cyclase → cAMP/PKA → increased GH mRNA transcription and vesicle exocytosis. This determines the amplitude of each GH pulse.
• Ipamorelin → GHS-R1a (Ghrelin Receptor): Gq/11-coupled receptor activation → PLC → IP3/DAG → intracellular Ca²⁺ release → GH vesicle fusion. This determines the frequency of GH pulses.

The two receptors converge on the same somatotroph cell but through different intracellular signaling pathways (cAMP vs Ca²⁺). This is why the combination produces synergistic rather than additive GH release — both the amplitude and frequency of GH pulses are simultaneously enhanced.

Selectivity advantage: Both CJC-1295 and Ipamorelin are highly selective. CJC-1295 does not activate cortisol or prolactin release (unlike CRH or TRH). Ipamorelin does not increase cortisol, prolactin, or appetite (unlike GHRP-6 which activates all three). The combination produces the cleanest possible GH signal from secretagogue peptides.

Reconstitution procedure: Select bacteriostatic water (0.9% benzyl alcohol in sterile water) as the standard diluent for research applications; sterile water or 0.9% saline may also be used when a preservative-free vehicle is required for in vitro assays. Calculate diluent volume based on the desired working concentration — for example, adding 2 mL of diluent to a 5 mg CJC-1295 / 5 mg Ipamorelin blended vial yields nominal concentrations of 2.5 mg/mL for each peptide.

Technique:

• Allow both the lyophilized vial and the diluent to reach room temperature before opening to avoid condensation on cold glass surfaces.
• Wipe the vial septum with 70% isopropanol and allow to air-dry.
• Draw the diluent into a sterile syringe and inject it slowly down the inner glass wall of the vial rather than directly onto the peptide cake. The shear forces of a direct jet can mechanically disrupt the lyophilized matrix and promote aggregation.
• Allow the vial to stand undisturbed for 5-10 minutes. Gently swirl or roll between the palms — do not shake or vortex aggressively, as foaming introduces air-water interfaces that denature peptides and accelerate aggregation.
• Inspect the reconstituted solution: it should be clear and colorless with no visible particulates. Discard any vial showing cloudiness, precipitate, or discoloration.

Blend-specific notes: Because the vial contains two peptides co-lyophilized in a single cake, complete dissolution of both components occurs simultaneously upon reconstitution. The molar ratio is fixed by the manufacturing fill, so investigators cannot independently titrate CJC-1295 versus Ipamorelin from a single blended vial. For experimental designs that require independent dose-response curves, staggered administration timing, or single-peptide control arms, AminoCore Research offers individual vials of CJC-1295 (no DAC) and Ipamorelin that can be reconstituted and dosed separately.

Aliquoting and storage post-reconstitution: For studies extending beyond 14 days, divide the reconstituted solution into single-use aliquots in low-protein-binding polypropylene tubes (e.g., Eppendorf LoBind) and store at -20°C or -80°C. Avoid repeated freeze-thaw cycles, which compromise peptide integrity through ice-crystal-induced denaturation and solute concentration effects. Label each aliquot with peptide identity, concentration, reconstitution date, and diluent lot for traceability.

Personal protective equipment: Standard laboratory PPE — nitrile gloves, lab coat, and safety glasses — should be worn during all reconstitution and handling steps. Work within a biosafety cabinet or clean laminar-flow hood when sterility is critical for downstream cell-culture or in vivo research applications.

For laboratory research use only.

Lyophilized powder: When stored desiccated at -20°C in the original sealed vial, the lyophilized CJC-1295 + Ipamorelin blend remains chemically stable for approximately 24 months. The lyophilization process removes residual water that would otherwise catalyze peptide-bond hydrolysis, deamidation of asparagine/glutamine residues, and oxidation of methionine or other susceptible side chains. Lower temperatures further slow these degradation pathways by reducing molecular motion and reaction kinetics.

Short-term ambient exposure: Brief transit at ambient temperature (commonly 3-7 days) generally does not compromise lyophilized peptide integrity because the dry-state matrix limits hydrolytic and oxidative chemistry. Upon receipt, vials should be transferred promptly to -20°C (or colder) for long-term archival storage.

Reconstituted solution: After reconstitution with bacteriostatic water (typically 0.9% benzyl alcohol), the solution should be stored at 2-8°C, protected from light, and used within approximately 14 days. Both CJC-1295 (Mod GRF 1-29) and Ipamorelin share similar aqueous-phase stability profiles in this temperature range. Bacteriostatic water suppresses microbial growth but does not arrest chemical degradation; therefore, reconstituted aliquots gradually accumulate des-amido, oxidized, and truncated species over time.

Stability considerations specific to the blend:

• CJC-1295 (no DAC): The four amino-acid substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) confer resistance to dipeptidyl peptidase-IV (DPP-IV) and trypsin-like proteases, improving stability relative to native GHRH(1-29) in solution.
• Ipamorelin: A pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) with C-terminal amidation and non-natural residues, providing relatively high chemical and enzymatic robustness in aqueous buffer.
• Co-formulation: No published evidence of adverse peptide-peptide interactions, precipitation, or cross-degradation in the blended lyophilizate at standard research concentrations.

Handling best practices: Protect both lyophilized and reconstituted material from direct light (UV exposure accelerates oxidation of aromatic residues). Avoid repeated freeze-thaw cycles of reconstituted solution, as ice-crystal formation can denature peptide structure and concentrate solutes at phase boundaries. For protocols requiring multiple withdrawals, prepare single-use aliquots in low-bind polypropylene tubes and store at -20°C or -80°C. Always equilibrate frozen aliquots to 2-8°C before opening to minimize condensation on cold surfaces, which can introduce moisture and microbial contaminants. Document reconstitution date, diluent lot, and storage location on the vial for chain-of-custody and reproducibility purposes.

For laboratory research use only. Not for human or veterinary use.