2x CJC-1295 No DAC Bundle

Growth-hormone-releasing hormone is a 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. Native GHRH(1-29), also known as sermorelin, retains full receptor engagement in research models but is rapidly inactivated by dipeptidyl peptidase-IV (DPP-IV) cleavage at the N-terminal Tyr-Ala bond and by other proteolytic mechanisms, producing a plasma residency window of only a few minutes. This kinetic constraint limited laboratory investigations of GHRH-receptor signaling dynamics and motivated the design of sequence-stabilized analogs.

CJC-1295 No DAC was developed as a synthetic GHRH(1-29) analog incorporating four amino-acid substitutions: D-Ala at position 2 (DPP-IV resistance), Gln at position 8 (asparagine-rearrangement resistance), Ala at position 15 (enhanced receptor engagement), and Leu at position 27 (methionine-oxidation resistance). Unlike the DAC-conjugated variant, CJC-1295 No DAC lacks the C-terminal maleimidopropionyl-lysine albumin-binding linker, producing a plasma residency window of approximately 30 minutes, substantially longer than native GHRH(1-29) but much shorter than the multi-day window of the DAC-conjugated analog.

This intermediate-residency profile has made CJC-1295 No DAC a widely studied reference compound for laboratory investigations of pulsatile GHRH-receptor engagement, somatotropic-axis pulse-amplitude research, and comparative pharmacology versus both native GHRH(1-29) and the DAC-conjugated analog. Research interest spans pituitary somatotroph signaling models, hypothalamic-pituitary feedback research, and structure-activity studies on GHRH analog design.

CJC-1295 No DAC Structure

1. GHRH-Receptor Engagement on Pituitary Somatotrophs

CJC-1295 No 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 comparable to native GHRH(1-29) but with extended plasma residency due to the sequence-level modifications (Ionescu & Frohman, 2006, JCEM).

2. Modulation of Cyclic AMP and Downstream Kinases

Upon receptor engagement, CJC-1295 No 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. Sequence-Stabilized Plasma Residency

The four amino-acid substitutions confer resistance to DPP-IV cleavage and other proteolytic mechanisms, extending plasma residency from minutes for native GHRH(1-29) to approximately 30 minutes in research models, without the multi-day extension produced by albumin bioconjugation in the DAC-conjugated variant.

4. Pulsatile-Preserving Signaling Pattern

Laboratory research studies have characterized CJC-1295 No DAC as engaging the GHRH receptor in a manner that produces discrete pulse-amplitude signaling in research models, rather than the prolonged tonic engagement profile of the DAC-conjugated analog. This pulse-preserving profile is an active area of structure-activity research and is investigated as a contributor to comparative somatotropic-axis dynamics versus longer-residency analogs.

Research Applications

Conclusion

CJC-1295 No DAC represents a sequence-stabilized GHRH(1-29) analog that occupies an intermediate-residency position between native GHRH(1-29) and the DAC-conjugated variant. Its four amino-acid substitutions confer resistance to proteolytic degradation without the multi-day extension of albumin bioconjugation, making it a valuable investigational laboratory peptide for studying pulsatile GHRH-receptor engagement, somatotropic-axis pulse dynamics, and structure-activity relationships in GHRH analog design.