CJC-1295 (No DAC) and Ipamorelin: Dual GH-Axis Receptor Research
Scientific Rationale for Dual-Receptor Investigation
The growth hormone axis is regulated by two primary receptor systems: the growth hormone-releasing hormone receptor (GHRH-R) and the growth hormone secretagogue receptor type 1a (GHS-R1a). CJC-1295 No DAC and Ipamorelin are synthetic peptide agonists targeting these two receptor subtypes respectively, and their co-administration has been investigated in preclinical models examining the effects of concurrent receptor activation.
CJC-1295 No DAC (Modified GRF 1-29)
Discovery and Structure
CJC-1295 No DAC, also designated Modified GRF(1-29) or tetrasubstituted GRF(1-29), is a 30-amino acid synthetic analog of endogenous growth hormone-releasing hormone. The "No DAC" designation indicates this formulation does not contain the Drug Affinity Complex—a maleimidopropionic acid linker used in some formulations to enable covalent albumin binding.
The peptide (MW ~3,368 Da) contains four amino acid substitutions relative to native GHRH(1-29):
- D-Ala² — confers resistance to DPP-IV enzymatic cleavage at the N-terminus
- Gln⁸ — replaces asparagine to prevent deamidation
- Ala¹⁵ — stabilizes the α-helical conformation
- Leu²⁷ — enhances receptor binding affinity
These modifications extend the compound's stability in biological media while preserving GHRH receptor binding characteristics.
Ipamorelin
Discovery and Structure
Ipamorelin was developed at Novo Nordisk in the 1990s as part of a systematic effort to create highly selective growth hormone secretagogue receptor agonists. It is a synthetic pentapeptide (MW ~712 Da) with the sequence Aib-His-D-2Nal-D-Phe-Lys-NH₂, incorporating several non-natural amino acids including alpha-aminoisobutyric acid (Aib) and D-2-naphthylalanine (D-2Nal).
Selectivity Profile
Ipamorelin is notable in preclinical literature for its selectivity. Unlike earlier GHS-R1a agonists such as GHRP-6 and GHRP-2, which stimulated release of multiple pituitary hormones, ipamorelin demonstrated selective GH release without significant effects on adrenocorticotropic hormone (ACTH), cortisol, or prolactin levels in in vitro pituitary cell studies.
Dual-Receptor Research
The combination of GHRH-R and GHS-R1a agonists has been studied to investigate synergistic receptor activation on the somatotroph cell population. The theoretical basis is that GHRH primarily acts through Gs-protein-coupled cAMP signaling, while ghrelin/GHS-R1a signals through Gq-protein-coupled phospholipase C/IP₃/calcium pathways. Concurrent activation of both pathways may produce effects not achievable through either pathway alone.
Future Research Directions
Active areas include characterization of the signaling crosstalk between GHRH-R and GHS-R1a pathways at the molecular level, investigation of potential receptor heterodimer formation, and comparative studies of different GHRH-R/GHS-R1a agonist combinations.
Available at Crush Research: CJC-1295/Ipamorelin 10mg and 20mg blends, plus standalone Ipamorelin 10mg. View Certificates of Analysis.
All products are intended for in vitro and laboratory research use only. Not for human or veterinary use.