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Conclusion and Implications The novel orally active compounds show potent and effective SST4 receptor agonism in vitro and in vivo. All four novel ligands proved to be full agonists based on G protein activation, but failed to recruit β-arrestin. Based on their potent antinociceptive effect in the neuropathic pain model following a single oral administration, they are promising candidates for drug development.The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing "COVID-19" pandemics has been marked as