Sermorelin Acetate

Sermorelin Acetate is synthetic human GHRH(1-29)-NH2 — the 29 amino acid N-terminal fragment of endogenous growth hormone releasing hormone (GHRH) retaining complete GHRHR agonist activity. As the unmodified native sequence without the stability modifications incorporated in CJC-1295 variants, Sermorelin is the foundational reference compound for GHRHR pharmacology research, providing the authentic native pharmacophore for comparison against stabilised analogues.

Endogenous GHRH is a 44 amino acid peptide produced by hypothalamic arcuate nucleus neurons. Research beginning in the 1980s established that GHRH(1-29) contains the complete receptor pharmacophore — the remaining 15 C-terminal residues contribute to binding affinity but are not required for GHRHR activation. Sermorelin was developed as the minimal active fragment and became the first clinically used GHRH analogue, approved as Geref by Serono for GH deficiency diagnostics and paediatric GH insufficiency treatment before commercial withdrawal in 2002 (for business rather than safety reasons).

The primary limitation of Sermorelin as a research tool is its short plasma half-life of approximately 10-20 minutes, attributable to DPP-IV (dipeptidyl peptidase IV) cleavage at the Ala2-Asp3 bond. DPP-IV is a serine protease expressed at high density on endothelial cell surfaces and circulating lymphocytes, making plasma Ala-X bond cleavage extremely rapid. The resulting inactive GHRH(3-29) fragment has no GHRHR binding activity. This DPP-IV sensitivity is both a research limitation (requiring more frequent dosing or stable analogue alternatives for chronic experiments) and a research tool (enabling direct quantification of DPP-IV contribution to GHRH half-life by comparing Sermorelin with CJC-1295 No DAC at matched molar doses).

GHRHR structure: Sermorelin activates the class B GPCR (secretin receptor family) through a two-step mechanism characteristic of this receptor family. The large N-terminal extracellular domain (ECD) of GHRHR captures the C-terminal portion of the GHRH peptide, and the N-terminal GHRH pharmacophore (Tyr1-Ala2-Asp3-Ala4-Ile5-Phe6) then engages the transmembrane domain to activate Gs. This explains why GHRH(1-29) retains full activity — the N-terminal pharmacophore is intact — while the C-terminal ECD-binding region is truncated.

Published clinical pharmacology from Sermorelin stimulation test data (used diagnostically to assess pituitary GH reserve): intravenous Sermorelin produces peak GH at 15-30 minutes, return to baseline by 60-90 minutes, and peak GH correlates with pituitary somatotroph functional mass. This published dataset provides translational reference for laboratory pituitary cell research using Sermorelin.

Direct Sermorelin versus CJC-1295 No DAC comparison research: in serum-containing pituitary cell culture at 37°C, Sermorelin undergoes approximately 50% degradation within 20 minutes — measurable as reduced GH-releasing potency over extended incubation periods compared to CJC-1295 No DAC. Quantifying this potency shift directly characterises the pharmacological benefit of DPP-IV resistance in pituitary research models.

MW: 3357.88 g/mol. CAS: 86168-78-7. Molecular formula: C149H246N44O42S. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.

DPP-IV sensitivity quantification: to directly measure Sermorelin's DPP-IV degradation in research conditions, incubate Sermorelin (100nM) in 25% human plasma at 37°C for 0, 5, 10, 20, 30, 60 minutes. Analyse remaining intact Sermorelin by LC-MS/MS (MRM transitions for the intact peptide vs the DPP-IV cleavage product GHRH 3-29). Run the identical experiment with CJC-1295 No DAC at matched molar concentration. The time-course comparison directly quantifies the pharmacological benefit of D-Ala2 modification in your specific research matrix. DPP-IV inhibitor control: add sitagliptin (10uM) to the plasma incubation to confirm that observed Sermorelin degradation is DPP-IV-dependent. This plasma stability assay is a recommended pre-experiment quality control for all GHRH analogue comparative research. MW: 3357.88 g/mol. CAS: 86168-78-7. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.