Binding of the small-molecule kinase inhibitor ruxolitinib to membranes does not disturb membrane integrity

小分子激酶抑制剂芦可替尼与膜结合不会破坏膜完整性

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作者:Markus Fischer, Meike Luck, Maximilian Werle, Holger A Scheidt, Peter Müller

Abstract

Ruxolitinib is a small-molecule protein kinase inhibitor, which is used as a therapeutic agent against several diseases. Due to its anti-inflammatory impact, ruxolitinib has also been considered recently for usage in the treatment of Covid-19. While the specific effects of ruxolitinib on Janus kinases (JAK) is comparatively well investigated, its (unspecific) impact on membranes has not been studied in detail so far. Therefore, we characterized the interaction of this drug with lipid membranes employing different biophysical approaches. Ruxolitinib incorporates into the glycerol region of lipid membranes causing an increase in disorder of the lipid chains. This binding, however, has only marginal influence on the structure and integrity of membranes as found by leakage and permeation assays.

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