CJC-1295 No DAC + Ipamorelin Blend: Research Overview

CJC-1295 No DAC + Ipamorelin Blend: Research Overview

Overview

The CJC-1295 No DAC + Ipamorelin blend is a lyophilized research peptide formulation combining CJC-1295 No DAC (5 mg; also designated Mod GRF 1-29 or Modified GRF(1-29)) and Ipamorelin (5 mg) in a single 10 mg vial. Each component has been characterized independently in the peer-reviewed literature and represents a distinct mechanistic approach to the pituitary GH secretory axis. CJC-1295 No DAC is a DPP-IV–stabilized analog of growth hormone-releasing hormone (GHRH), acting at the GHRH receptor (GHRHR) through the adenylyl cyclase / cAMP / PKA second-messenger pathway. Ipamorelin is a selective synthetic pentapeptide agonist of the ghrelin / growth hormone secretagogue receptor type 1a (GHS-R1a), engaging the phospholipase C / IP₃ / Ca²⁺ pathway.

The research rationale for combining these two compounds is mechanistic: GHRHR and GHS-R1a are distinct receptors expressed on the same anterior pituitary somatotroph cells, and simultaneous stimulation of both pathways produces a supra-additive elevation in GH release compared to either compound alone — a phenomenon originally characterized by Bowers et al. (1990; PMID: 2108187) using earlier GHRP-class secretagogue peptides paired with GHRH in both rodent and human subjects. Combining a stabilized GHRH analog with a selective GHS-R1a agonist in a single formulation provides a well-defined two-component research model for studying dual-pathway GH axis activation.

Note on published pharmacology: The majority of published human pharmacokinetic and pharmacodynamic data for the CJC-1295 scaffold is derived from studies on the with-DAC (Drug Affinity Complex) form — CJC-1295 with DAC (CAS 863971-19-1), which has an extended half-life due to covalent albumin binding. CJC-1295 No DAC (Mod GRF 1-29; CAS 863288-34-0) lacks the DAC moiety and has distinct pharmacokinetics, though the two forms share the same GHRH-receptor agonist mechanism. Researchers should consult literature carefully to distinguish between data on the DAC and No-DAC forms.


Component Molecular Profiles

CJC-1295 No DAC (Mod GRF 1-29)

CAS Number 863288-34-0
Molecular Formula C₁₅₂H₂₅₂N₄₄O₄₂
Molecular Weight 3367.95 g/mol
Alternative Names Mod GRF 1-29; Modified GRF(1-29); CJC-1295 without DAC
Structure GHRH(1-29) analog with four stabilizing substitutions: D-Ala², Gln⁸, Ala¹⁵, Leu²⁷

Ipamorelin

CAS Number 170851-70-4
Molecular Formula C₃₈H₄₉N₉O₅
Molecular Weight 711.85 g/mol
Alternative Names NNC 26-0161
Sequence Aib-His-D-2-Nal-D-Phe-Lys-NH₂ (pentapeptide)

Mechanism of Action

CJC-1295 No DAC: GHRH-Receptor Pathway

CJC-1295 No DAC is an analog of human GHRH(1-29)-NH₂, the N-terminal fragment of hypothalamic GHRH(1-44)-NH₂ that retains full receptor-binding activity. Four amino acid substitutions — D-Ala at position 2, Gln at position 8, Ala at position 15, and Leu at position 27 — confer resistance to dipeptidyl peptidase-IV (DPP-IV)–mediated cleavage at the Tyr¹-Ala² bond, the primary enzymatic degradation site for native GHRH(1-29). The result is a DPP-IV–resistant GHRH analog that retains full GHRHR agonism.

Binding of CJC-1295 No DAC to the GHRH receptor (GHRHR), a class B G protein-coupled receptor on pituitary somatotrophs, activates Gαs-coupled adenylyl cyclase, generating cyclic AMP (cAMP) and activating protein kinase A (PKA). PKA-mediated phosphorylation of key transcription factors and ion channels increases intracellular Ca²⁺ and drives exocytosis of GH secretory granules, while also stimulating transcription of the GH gene.

Ipamorelin: GHS-R1a Pathway

Ipamorelin is a selective synthetic agonist of GHS-R1a, the ghrelin receptor. GHS-R1a couples to Gαq, activating phospholipase C (PLC) to generate IP₃ and DAG. IP₃ mobilizes intracellular Ca²⁺ from the endoplasmic reticulum, triggering GH granule exocytosis in the same somatotroph cell through a pathway mechanistically distinct from the cAMP pathway engaged by GHRHR.

Dual-Pathway Supra-Additive GH Release

Because GHRHR and GHS-R1a signal through distinct second-messenger cascades (cAMP/PKA vs. PLC/Ca²⁺), their simultaneous activation produces GH release greater than the sum of either agonist alone — a supra-additive response originally described by Bowers et al. (1990; PMID: 2108187) in rodents and human subjects using GHRH paired with GHRP-class peptides. This mechanistic complementarity is the primary research rationale for formulating a GHRH analog (CJC-1295 No DAC) and a GHS-R1a agonist (ipamorelin) as a combination research tool.

Key Areas of Investigation

GHRH Receptor Pharmacology and DPP-IV Resistance

The enzymatic instability of native GHRH(1-29) — with a plasma half-life of approximately 2 minutes due to DPP-IV cleavage — has motivated substantial interest in DPP-IV–resistant GHRH analogs as research tools for controlled GH-axis stimulation studies. The four-substitution strategy in Mod GRF 1-29 / CJC-1295 No DAC extends the effective half-life to a range more suitable for standard subcutaneous dosing paradigms without altering GHRHR pharmacology. This DPP-IV–stabilized scaffold shares its core receptor-level mechanism with the extensively characterized CJC-1295 with-DAC compound studied by Teichman et al. (2006; PMID: 16352683), which demonstrated sustained dose-dependent GH and IGF-1 stimulation over multi-day intervals in a randomized controlled study, though the DAC form’s prolonged kinetics differ substantially from the No-DAC form.

Dual GH-Axis Stimulation: GHRP + GHRH Combination Models

The foundational characterization of GHRH + GHRP synergy by Bowers et al. (1990; PMID: 2108187) has informed a wide body of preclinical research examining pulsatile GH restoration models. In that study, co-administration of GHRH and GHRP in normal men produced GH release that exceeded the sum of each compound administered alone, consistent with two non-competing second-messenger pathways converging on the same somatotroph population. Subsequent preclinical and early clinical work has used various GHRH-class + GHRP-class pairings to model the GH secretory dynamics of younger or healthier physiological states, with the CJC-1295 No DAC + ipamorelin combination representing a well-characterized instance of this research strategy.

GH/IGF-1 Axis Downstream Endpoints in Preclinical Models

Research using GHRH-analog + GHRP combinations has examined downstream GH/IGF-1 axis responses including serum IGF-1 and IGFBP-3 dynamics, body composition endpoints (muscle cross-sectional area, intramuscular fat, visceral adipose tissue), and GH pulse characteristics (peak amplitude, pulse frequency, trough levels). These endpoints serve as functional readouts of GH-axis stimulation intensity and are used in preclinical systems to distinguish the effects of different GHRH/GHRP dose ratios and pairing strategies.

Key Published References

  1. Bowers CY, Reynolds GA, Durham D, et al. Growth hormone (GH)-releasing peptide stimulates GH release in normal men and acts synergistically with GH-releasing hormone. J Clin Endocrinol Metab. 1990;70(4):975–982. PMID: 2108187
  2. Teichman SL, Neale A, Lawrence B, et al. 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. PMID: 16352683 (DAC form; cited for shared GHRHR mechanism)
  3. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552–561. PMID: 9849822

Related Research

For published research on the individual components, see: Ipamorelin Research Overview and Tesamorelin Research Overview (a clinically characterized GHRH analog from the same receptor class).

Product Availability

CJC-1295 No DAC + Ipamorelin (10 mg) is available for qualified research applications through White Market Peptides: CJC-1295 No DAC + Ipamorelin 10 mg: Research Grade.

Research Use Only. This product is sold exclusively for in vitro research and laboratory use. It is not intended for human or animal consumption, clinical use, or veterinary applications, and has not been evaluated by the FDA. Not intended to diagnose, treat, cure, or prevent any disease. All information presented is for research and educational purposes only. Use is restricted to qualified researchers in compliance with applicable local, state, and federal regulations.

Available for Research

CJC-1295 No DAC + Ipamorelin (10 mg)

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