Drug repurposing for cardiovascular diseases: New targets and indications for probenecid

doi:10.1111/bph.16001

Review

. 2023 Mar;180(6):685-700.

doi: 10.1111/bph.16001. Epub 2022 Dec 26.

Drug repurposing for cardiovascular diseases: New targets and indications for probenecid

Zsófia Onódi^{1

2

3}, Sheryl Koch⁴, Jack Rubinstein⁴, Péter Ferdinandy^{1

5}, Zoltán V Varga^{1

2

3}

Affiliations

¹ Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
² HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University, Budapest, Hungary.
³ MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Semmelweis University, Budapest, Hungary.
⁴ Department of Internal Medicine, Division of Cardiovascular Health and Disease, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
⁵ Pharmahungary Group, Szeged, Hungary.

PMID: 36484549
DOI: 10.1111/bph.16001

Free article

Review

Drug repurposing for cardiovascular diseases: New targets and indications for probenecid

Zsófia Onódi et al. Br J Pharmacol. 2023 Mar.

Free article

. 2023 Mar;180(6):685-700.

doi: 10.1111/bph.16001. Epub 2022 Dec 26.

Authors

Zsófia Onódi^{1

2

3}, Sheryl Koch⁴, Jack Rubinstein⁴, Péter Ferdinandy^{1

5}, Zoltán V Varga^{1

2

3}

Affiliations

¹ Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
² HCEMM-SU Cardiometabolic Immunology Research Group, Semmelweis University, Budapest, Hungary.
³ MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Semmelweis University, Budapest, Hungary.
⁴ Department of Internal Medicine, Division of Cardiovascular Health and Disease, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
⁵ Pharmahungary Group, Szeged, Hungary.

PMID: 36484549
DOI: 10.1111/bph.16001

Abstract

The available pharmacological options in the management of cardiovascular diseases such as ischaemic heart disease and subsequent heart failure are effective in slowing the progression of this condition. However, the long-term prognosis is still poor, raising the demand for new therapeutic strategies. Drug repurposing is a time- and cost-effective drug development strategy that offers approved and abandoned drugs a new chance for new indications. Recently, drugs used for the management of gout-related inflammation such as canakinumab or colchicine have been considered for drug repurposing in cardiovascular indications. The old uricosuric drug, probenecid, has been identified as a novel therapeutic option in the management of specific cardiac diseases as well. Probenecid can modulate myocardial contractility and vascular tone and exerts anti-inflammatory properties. The mechanisms behind these beneficial effects might be related inhibition of inflammasomes, and to modulation purinergic-pannexin-1 signalling and TRPV2 channels, which are recently identified molecular targets of probenecid. In this review, we provide an overview on repurposing probenecid for ischaemic heart disease and subsequent heart failure by summarizing the related experimental and clinical data and propose its potential repurposing to treat cardiovascular diseases.

Keywords: drug repositioning; heart failure; inflammation; pannexin-1; probenecid.

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References

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1. Adamo, L., Rocha-Resende, C., Prabhu, S. D., & Mann, D. L. (2020). Reappraising the role of inflammation in heart failure. Nature Reviews. Cardiology, 17(5), 269-285. https://doi.org/10.1038/s41569-019-0315-x
1. Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., … Ye, R. D. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. British Journal of Pharmacology, 178(S1), S27-S156. https://doi.org/10.1111/bph.15538
1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., … Waldman, S. A. (2021a). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Catalytic receptors. British Journal of Pharmacology, 178(S1), S264-S312. https://doi.org/10.1111/bph.15541
1. Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Boison, D., Burns, K. E., Dessauer, C., Gertsch, J., Helsby, N. A., Izzo, A. A., Koesling, D., … Wong, S. S. (2021b). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. British Journal of Pharmacology, 178(S1), S313-S411. https://doi.org/10.1111/bph.15542

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[1] Abbate, A., Kontos, M. C., Abouzaki, N. A., Melchior, R. D., Thomas, C., van Tassell, B. W., Oddi, C., Carbone, S., Trankle, C. R., Roberts, C. S., Mueller, G. H., Gambill, M. L., Christopher, S., Markley, R., Vetrovec, G. W., Dinarello, C. A., & Biondi-Zoccai, G. (2015). Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). The American Journal of Cardiology, 115(3), 288-292. https://doi.org/10.1016/j.amjcard.2014.11.003

[2] Abbate, A., Kontos, M. C., Abouzaki, N. A., Melchior, R. D., Thomas, C., van Tassell, B. W., Oddi, C., Carbone, S., Trankle, C. R., Roberts, C. S., Mueller, G. H., Gambill, M. L., Christopher, S., Markley, R., Vetrovec, G. W., Dinarello, C. A., & Biondi-Zoccai, G. (2015). Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). The American Journal of Cardiology, 115(3), 288-292. https://doi.org/10.1016/j.amjcard.2014.11.003

[3] Adamo, L., Rocha-Resende, C., Prabhu, S. D., & Mann, D. L. (2020). Reappraising the role of inflammation in heart failure. Nature Reviews. Cardiology, 17(5), 269-285. https://doi.org/10.1038/s41569-019-0315-x

[4] Adamo, L., Rocha-Resende, C., Prabhu, S. D., & Mann, D. L. (2020). Reappraising the role of inflammation in heart failure. Nature Reviews. Cardiology, 17(5), 269-285. https://doi.org/10.1038/s41569-019-0315-x

[5] Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., … Ye, R. D. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. British Journal of Pharmacology, 178(S1), S27-S156. https://doi.org/10.1111/bph.15538

[6] Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Abbracchio, M. P., Alexander, W., Al-hosaini, K., Bäck, M., Barnes, N. M., Bathgate, R., … Ye, R. D. (2021). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors. British Journal of Pharmacology, 178(S1), S27-S156. https://doi.org/10.1111/bph.15538

[7] Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., … Waldman, S. A. (2021a). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Catalytic receptors. British Journal of Pharmacology, 178(S1), S264-S312. https://doi.org/10.1111/bph.15541

[8] Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Beuve, A., Brouckaert, P., Bryant, C., Burnett, J. C., Farndale, R. W., Friebe, A., Garthwaite, J., … Waldman, S. A. (2021a). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Catalytic receptors. British Journal of Pharmacology, 178(S1), S264-S312. https://doi.org/10.1111/bph.15541

[9] Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Boison, D., Burns, K. E., Dessauer, C., Gertsch, J., Helsby, N. A., Izzo, A. A., Koesling, D., … Wong, S. S. (2021b). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. British Journal of Pharmacology, 178(S1), S313-S411. https://doi.org/10.1111/bph.15542

[10] Alexander, S. P., Fabbro, D., Kelly, E., Mathie, A., Peters, J. A., Veale, E. L., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Southan, C., Davies, J. A., Boison, D., Burns, K. E., Dessauer, C., Gertsch, J., Helsby, N. A., Izzo, A. A., Koesling, D., … Wong, S. S. (2021b). THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Enzymes. British Journal of Pharmacology, 178(S1), S313-S411. https://doi.org/10.1111/bph.15542

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Drug repurposing for cardiovascular diseases: New targets and indications for probenecid

Affiliations

Drug repurposing for cardiovascular diseases: New targets and indications for probenecid

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Affiliations

Abstract

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Abstract

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