CJC-1295 (No DAC) + Ipamorelin (20 mg) (Blend)

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.

The growth-hormone secretagogue receptor (GHS-R1a) was identified as the endogenous receptor for ghrelin, a 28-amino-acid acylated peptide involved in somatotropic-axis signaling and metabolic research. Early non-selective GHS research peptides (GHRP-6, GHRP-2, hexarelin) engaged GHS-R1a but also produced collateral activity at other endocrine pathways, limiting their utility as receptor-selective research tools.

Ipamorelin was developed by Novo Nordisk researchers as a five-residue scaffold designed to selectively engage GHS-R1a while minimizing collateral receptor activity. Structural studies and receptor-binding research established the pentapeptide as a high-affinity, high-selectivity GHS-R agonist suitable for laboratory investigation of receptor-mediated signaling.

This positioning at the intersection of ghrelin-receptor signaling research, selective GPCR pharmacology, and somatotropic-axis research models has made Ipamorelin a peptide of considerable interest in laboratory investigations of GHS-R1a biology and downstream growth-hormone-pathway dynamics.

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.

1. Selective GHS-R1a Engagement

Ipamorelin binds the growth-hormone secretagogue receptor (GHS-R1a, the ghrelin receptor), a Gq-coupled class A GPCR expressed on anterior-pituitary somatotrophs and selected peripheral tissues. Receptor engagement activates phospholipase-C, generates inositol-1,4,5-trisphosphate, and mobilizes intracellular calcium in laboratory research models.

2. Ghrelin-Receptor Signaling Research

Through GHS-R1a engagement, Ipamorelin is investigated as a probe for ghrelin-receptor-coupled signaling, including PLC/IP3/Ca2+ mobilization, MAPK pathway activation, and downstream transcriptional research in somatotroph cellular models.

3. Selectivity Profile in Receptor Research

Receptor-binding studies have characterized Ipamorelin as engaging GHS-R1a with minimal activity at adjacent endocrine receptor pathways. In laboratory research models, this selectivity is associated with absence of appreciable ACTH, cortisol, prolactin, or aldosterone receptor signaling, distinguishing it from earlier non-selective GHS research peptides.

4. Somatotropic-Axis Research Models

Ipamorelin is investigated alongside GHRH-receptor agonists (e.g., Sermorelin, CJC-1295, Tesamorelin) to study receptor-coupled signaling interactions between the GHS-R1a and GHRH-R pathways in controlled laboratory research.

Research Applications

Conclusion

Ipamorelin represents a structurally defined pentapeptide research compound that selectively engages the GHS-R1a (ghrelin) receptor. By providing high receptor selectivity within the somatotropic-axis research framework, it serves as a useful tool compound for examining ghrelin-receptor signaling research, selective GPCR pharmacology, and downstream growth-hormone-pathway dynamics in controlled laboratory models.