Ikarugamycin: A Natural Product Inhibitor of Clathrin‐Mediated Endocytosis

Ikarugamycin ( IKA ) is a previously discovered antibiotic, which has been shown to inhibit the uptake of oxidized low‐density lipoproteins in macrophages. Furthermore, several groups have previously used IKA to inhibit clathrin‐mediated endocytosis ( CME ) in plant cell lines. However, detailed characterization of IKA has yet to be performed. Consequently, we performed biochemistry and microscopy experiments to further characterize the effects of IKA on CME . We show that IKA has an IC 50 of 2.7 μ m in H1299 cells and acutely inhibits CME , but not other endocytic pathways, in a panel of cell lines. Although long‐term incubation with IKA has cytotoxic effects, the short‐term inhibitory effects on CME are reversible. Thus, IKA can be a useful tool for probing routes of endocytic trafficking.