Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry pathway.
Nature Publishing Group
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Rahman, S., & Rahman, M. T. (2017). Unveiling some FDA-approved drugs as inhibitors of the store-operated Ca2+ entry pathway.. Scientific reports, 7 (1), 12881. https://doi.org/10.1038/s41598-017-13343-x
The store-operated calcium entry (SOCE) pathway is an important route for generating cytosolic Ca2+ signals that regulates a diverse array of biological processes. Abnormal SOCE seem to underlie several diseases that notably include allergy, inflammation and cancer. Therefore, any modulator of this pathway is likely to have significant impact in cell biology under both normal and abnormal conditions. In this study, we screened the FDA-approved drug library for agents that share significant similarity in 3D shape and surface electrostatics with few, hitherto best known inhibitors of SOCE. This has led to the identification of five drugs that showed dose-dependent inhibition of SOCE in cell-based assay, probably through interacting with the Orai1 protein which effectively mediates SOCE. Of these drugs, leflunomide and teriflunomide could suppress SOCE significantly at clinically-relevant doses and this provides for an additional mechanism towards the therapeutic utility of these drugs as immunosuppressants. The other three drugs namely lansoprazole, tolvaptan and roflumilast, were less potent in suppressing SOCE but were more selective and thus they may serve as novel scaffolds for future development of new, more efficacious SOCE inhibitors.
Hela Cells, Cell Nucleus, Animals, Humans, Rats, Calcium, Anilides, Thapsigargin, Thiadiazoles, Ligands, Biological Assay, Drug Approval, Drug Evaluation, Preclinical, Ion Channel Gating, Calcium Signaling, Protein Transport, United States Food and Drug Administration, User-Computer Interface, United States, NFATC Transcription Factors, Protein Multimerization, HEK293 Cells, Stromal Interaction Molecule 1, ORAI1 Protein
Royal Society (uf110479)
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External DOI: https://doi.org/10.1038/s41598-017-13343-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270639
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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