Luciferin and derivatives as a DYRK selective scaffold for the design of protein kinase inhibitors

European Journal of Medicinal Chemistry
Ulli RothweilerJohn S Svendsen

Abstract

D-Luciferin is widely used as a substrate in luciferase catalysed bioluminescence assays for in vitro studies. However, little is known about cross reactivity and potential interference of D-luciferin with other enzymes. We serendipitously found that firefly luciferin inhibited the CDK2/Cyclin A protein kinase. Inhibition profiling of D-luciferin over a 103-protein kinase panel showed significant inhibition of a small set of protein kinases, in particular the DYRK-family, but also other members of the CMGC-group, including ERK8 and CK2. Inhibition profiling on a 16-member focused library derived from D-luciferin confirms that D-luciferin represents a DYRK-selective chemotype of fragment-like molecular weight. Thus, observation of its inhibitory activity and the initial SAR information reported here promise to be useful for further design of protein kinase inhibitors with related scaffolds.

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Citations

Dec 15, 2015·Proceedings of the National Academy of Sciences of the United States of America·R Frederick LudlowHarren Jhoti
May 24, 2015·Biochimica Et Biophysica Acta·Osman A GaniRichard A Engh
Apr 14, 2016·Future Medicinal Chemistry·Silvia StotaniFederico Medda
Oct 14, 2016·Journal of Medicinal Chemistry·Ulli RothweilerJohn S Mjøen Svendsen
Nov 21, 2019·Pharmaceuticals·Anne Cecília Nascimento da CruzTeresinha Gonçalves da Silva
Aug 3, 2017·Expert Opinion on Therapeutic Patents·Thu Lan NguyenThierry Besson
Jul 6, 2019·Journal of Medicinal Chemistry·Christine YuehDima Kozakov
Aug 11, 2018·Journal of Medicinal Chemistry·Anna CzarnaUlli Rothweiler
Jan 30, 2020·Journal of Chemical Information and Modeling·Joseph KatigbakYingkai Zhang
Aug 28, 2021·International Journal of Molecular Sciences·Barbara PucelikAnna Czarna

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