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A3 Adenosine Receptor Ligands: From Discovery to Clinical Trials

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Purinergic Receptors and their Modulators

Part of the book series: Topics in Medicinal Chemistry ((TMC,volume 41))

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Abstract

Numerous classes of selective agonists, antagonists, and allosteric modulators of the A3 adenosine receptor (AR) have been reported. The structure–affinity relationships and selectivity of A3AR ligands compared to the other three ARs have been described. Furthermore, prodrugs of some of these ligands have been reported, and their efficacy was demonstrated in animal models. In recent years, a structural approach has been adopted for the discovery of novel A3AR ligands, either to improve the potency of known ligands or to discover novel chemotypes for this receptor. Some A3AR ligands are being developed as therapeutic candidate molecules for a variety of chronic (e.g., psoriasis, NASH, pain, cancer, glaucoma) and acute (stroke, cardiac ischemia) conditions. The number of current clinical trials for A3AR ligands has now grown, with A3AR agonists accounting for the majority. Both the historical development of this field and the current state of the clinical trial-directed medicinal chemistry are included in this chapter.

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Acknowledgments

We thank the NIDDK Intramural Res. Program (ZIADK031117) for support.

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The author declares that they have no conflict of interest.

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Not applicable.

Competing Interests

The authors declare no competing interests of a financial or personal nature.

Conflict of Interest

Kenneth A. Jacobson declares that he/she has no conflict of interest. Paola Oliva declares that he/she has no conflict of interest. R. Rama Suresh declares that he/she has no conflict of interest.

Authors’ Contributions

K.A.J., P.O. and R. R. S. wrote, edited, and reviewed the main manuscript text.

Funding

This work was supported by the Intramural Research Program of the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases for support [ZIADK031117 to K.A.J].

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Authors and Affiliations

  1. Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Kenneth A. Jacobson, Paola Oliva & R. Rama Suresh

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  1. Kenneth A. Jacobson
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  2. Paola Oliva
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  3. R. Rama Suresh
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Correspondence to Kenneth A. Jacobson .

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Editors and Affiliations

  1. Department of Neurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy

    Vittoria Colotta

  2. Department of Neurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Florence, Italy

    Claudiu T. Supuran

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Jacobson, K.A., Oliva, P., Suresh, R.R. (2023). A3 Adenosine Receptor Ligands: From Discovery to Clinical Trials. In: Colotta, V., Supuran, C.T. (eds) Purinergic Receptors and their Modulators. Topics in Medicinal Chemistry, vol 41. Springer, Cham. https://doi.org/10.1007/7355_2023_161

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