Hexarelin Acetate

Hexarelin Acetate (His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic hexapeptide growth hormone secretagogue and potent GHS-R1a agonist developed as part of the GHRP research programme. Hexarelin is the most potent GHS-R1a agonist in the GHRP series — producing higher peak GH release than GHRP-2 or GHRP-6 at equivalent molar concentrations — but also produces the most pronounced off-target effects including ACTH, cortisol, and prolactin stimulation.

The structural basis for Hexarelin's increased potency is the 2-methyltryptophan (2-MeTrp) substitution at position 2, replacing the D-Trp2 found in GHRP-6. This methylation of the indole nitrogen increases the binding affinity for GHS-R1a through enhanced hydrophobic contact with the receptor's orthosteric pocket, producing an EC50 for GH release approximately 3-5 fold lower than GHRP-6 in pituitary cell preparations.

GHS-R1a coupling in pituitary somatotrophs activates Gq/11, triggering phospholipase C-beta, IP3-mediated calcium release from the ER, and DAG/PKC activation. The calcium transient drives GH secretory granule exocytosis. Hexarelin's higher GHS-R1a affinity produces more complete receptor occupancy at a given concentration, explaining the greater peak GH release versus GHRP-2 or GHRP-6.

Beyond GH axis research, Hexarelin has been studied for direct cardiac receptor effects. Published research has identified specific hexarelin binding sites on cardiomyocytes distinct from GHS-R1a — potentially including CD36 (fatty acid translocase). These cardiac binding sites mediate direct cardioprotective effects in ischaemia-reperfusion injury models independently of GH release, positioning Hexarelin as a research tool for cardiac biology beyond the pituitary GH axis.

Comparative research using Hexarelin alongside Ipamorelin, GHRP-2, and GHRP-6 allows systematic characterisation of the GHS-R1a potency-selectivity trade-off across the GHRP series. Hexarelin provides the high-potency, low-selectivity end of the spectrum; Ipamorelin provides the high-selectivity, GH-specific end. This pharmacological range makes Hexarelin valuable for identifying GHS-R1a-independent components of GHRP biology.

For aged immune system restoration research: age-matched young (2-4 month) and old (18-24 month) C57BL/6 mouse splenocytes provide direct comparison material. Isolate splenocytes by mechanical disruption through a 70µm cell strainer. Red blood cell lysis with ACK buffer. Resuspend at 2×10^6 cells/mL. Treat with Thymalin (1-100µg/mL), Thymosin Alpha-1 (1-100nM), or vehicle for 72 hours with ConA stimulation (2.5µg/mL). Endpoints: proliferation (3H-thymidine, last 18 hours); IL-2 (ELISA, 24-hour supernatant); IFN-gamma (ELISA, 72-hour supernatant); NK cell cytotoxicity (non-adherent fraction, 51Cr release). If Thymalin restores aged splenocyte proliferative and cytokine responses toward young adult levels, this provides functional evidence for the immunorestoration hypothesis. Compare magnitude of restoration between Thymalin and Thymosin Alpha-1 to characterise relative potency of the polypeptide preparation versus the defined clinical compound. MW: approximately 1400-1500 Da. Reconstitute in bacteriostatic water at 1mg/mL. Store lyophilised at -20°C. For laboratory and analytical research purposes only.