BQ-3020 is a Selective ETB Receptor Agonist for Cardiovascular Disease Research

By Edward Jenner 2023-09-12 #Anti-Inflammatory, #BQ-3020, #cardiovascular, #Pain

ET_A and ET_B Receptor are isoforms of endothelin receptor. The ETA receptors on vascular smooth muscle cells mediate vasoconstriction. Otherwise, ET_B Receptor is present in both endothelial and vascular smooth muscle cells. Besides, ET_B receptor mediates the release of NO and prostanoids from endothelial cell. In addition, Endothelin is a vasoconstrictor endothelium-derived peptide. Endothelin has three isoforms called endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). Importantly, Endothelin acts on ETA and ETB receptors. Therefore, BQ3020, an ET-1 analog and the ET_Breceptor agonist, has great potential in cardiovascular disease research.

BQ-3020 is a potent and selective ET_B receptor agonist, and produce bladder neck smooth muscle relaxation.

In vitro, BQ-3020 displaces [¹²⁵I] ET-1 binding to ET_B receptor with an IC₅₀value of 0.2 nM. Besides, BQ-3020 can produce bladder neck smooth muscle relaxation. BQ-3020 elicits vasoconstriction in the rabbit pulmonary artery. BQ-3020 (0.01-300 nM, 7 min), produces concentration-dependent relaxations on PhE-precontracted urothelium-denuded strips. Similarly, BQ-3020 (0.01-00 nM, 20 min) also causes potent dose-dependent vasoconstriction with an EC₅₀ value of 0.57 nM in rabbit pulmonary arteries.

Moreover, BQ-3020 attenuates cancer pain in vivo. Specifically, in mice with squamous cell carcinoma (SCC) induced pain model, BQ-3020 (3 mg/kg for intratumor administration, single dose) attenuates cancer pain by approximately 50% up to 3 hours post-injection compared to PBS-vehicle and contralateral injection. In this model, BQ-3020 increases paw withdrawal thresholds compared to the control group.

Above all, BQ-3020 is a selective and potent ETB receptor agonist. BQ-3020 produces bladder neck smooth muscle relaxation. BQ-3020 also relieves pain in squamous cell carcinoma (SCC). BQ-3020 can be used for cardiovascular disease research.

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