2x CJC-1295 With DAC Bundle

Growth-hormone-releasing hormone is a 44-residue hypothalamic peptide that engages the GHRH receptor, a class B G-protein-coupled receptor expressed on pituitary somatotroph cells, and participates in growth-hormone-pathway investigation. For many years, research on GHRH analogs was limited by the very short plasma half-life of native GHRH(1-29), which is rapidly inactivated by dipeptidyl peptidase-IV (DPP-IV) cleavage and other proteolytic mechanisms. This kinetic limitation constrained laboratory investigations of sustained somatotropic-axis signaling and motivated the design of structurally modified analogs with improved plasma stability.

CJC-1295 With DAC was developed as a synthetic GHRH(1-29) analog incorporating four amino-acid substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) that confer resistance to proteolytic degradation, together with a C-terminal lysine bearing a maleimidopropionic acid (MPA) Drug Affinity Complex. The MPA group reacts selectively with the free cysteine-34 residue of serum albumin to form a stable covalent bioconjugate in research models, anchoring the peptide to a circulating carrier protein.

This dual structural strategy, sequence stabilization combined with albumin bioconjugation, has made CJC-1295 With DAC a widely studied reference compound for laboratory investigations of GHRH-receptor signaling kinetics, prolonged somatotropic-axis engagement, hepatic IGF-1 expression dynamics, and pharmacokinetic modeling of acylated peptide analogs. Research interest spans pituitary somatotroph signaling models, endocrine feedback research, and comparative pharmacology versus non-DAC GHRH analogs.

Synonyms: CJC-1295 (DAC-conjugated), DAC:GRF

1. GHRH-Receptor Engagement on Pituitary Somatotrophs

CJC-1295 With DAC engages the GHRH receptor on pituitary somatotroph cells, a class B G-protein-coupled receptor. Research models indicate that this engagement modulates Gαs-coupled signaling and adenylyl-cyclase activity, producing intracellular responses that have been compared with native GHRH(1-29) in laboratory studies (Jetté et al., 2005, Endocrinology).

2. Modulation of Cyclic AMP and Downstream Kinases

Upon receptor engagement, CJC-1295 With DAC modulates intracellular cyclic AMP accumulation. Downstream, this is associated with protein kinase A activation and CREB-mediated transcription, both of which are extensively studied in somatotropic-axis research as upstream regulators of growth-hormone gene expression in pituitary somatotroph models.

3. Albumin Bioconjugation and Extended Plasma Residency

The Nε-maleimidopropionyl-lysine modification enables covalent binding to the free cysteine-34 residue of serum albumin in research models. This structural feature is investigated in pharmacokinetics research as the basis for the peptide's extended plasma residency in laboratory species and is a frequent subject of comparative research versus non-acylated GHRH analogs.

4. Preserved Pulsatile Signaling Pattern

Laboratory research studies have characterized CJC-1295 With DAC as engaging the GHRH receptor in a manner that preserves the underlying pulsatile pattern of growth-hormone secretion in research models, rather than producing constant tonic stimulation. This pulsatile-preservation profile is an active area of structure-activity research.

Research Applications

Conclusion

CJC-1295 With DAC represents a structurally engineered GHRH(1-29) analog that has become a reference compound in somatotropic-axis research. Its combination of sequence-level stabilization (four amino-acid substitutions) and albumin bioconjugation through a maleimidopropionyl linker makes it a valuable investigational laboratory peptide for studying class B G-protein-coupled receptor pharmacology, growth-hormone-pathway investigation, and extended-residency peptide design.