PMC:7796052 / 15333-16631 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7796052","sourcedb":"PMC","sourceid":"7796052","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7796052","text":"4. Conclusions\nThe aim of the present study was to characterize the pharmacological profile of raloxifene towards the bradykinin receptors. The compound was identified as a micromolar ligand of the B2 receptor by virtual screening in a drug repurposing campaign. Results showed that raloxifene is a weak partial agonist toward the B2 receptor, with a 19% efficacy compared to bradykinin, with an apparent dissociation constant KB ~ 21 µM. The discovery of the bradykinin pharmacodynamics profile of raloxidene explains in part its observed vascular beneficial effects, although they could also be due to activation of the GPR30 receptor signaling pathway. On the other hand, it acts as a bradykinin antagonist for B2 with an IC50 ~ 21 µM.\nBased on the bradykinin hypothesis on the trigger of the cytokine storm in severe Covid-19 [12,13,14,15], these results suggest that the compound could be used for its treatment. Present results support previous claims suggesting the use of raloxifene based on its capacity to inhibit the IL-6/STAT3 signaling pathway [45], and also for being a prospective antiviral agent for SARS-Cov2 as inhibitor of the two-pore channel TCP2 [48]. Very recently a clinical trial in Italy has been approved to test its efficacy in COVID-19 patients with mild symptoms 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