Current therapies for common types of cancer such as renal cell cancer are often ineffective and unspecific, and novel pharmacological targets and approaches are in high demand. Here we show the unexpected possibility for the rapid and selective killing of renal cancer cells through activation of calcium‐permeable nonselective transient receptor potential canonical (TRPC) calcium channels by the sesquiterpene (−)‐englerin A. This compound was found to be a highly efficient, fast‐acting, potent, selective, and direct stimulator of TRPC4 and TRPC5 channels. TRPC4/5 activation through a high‐affinity extracellular (−)‐englerin A binding site may open up novel opportunities for drug discovery aimed at renal cancer.
Natural products play a dominant role in providing ligands that interfere with biopolymers such as receptors or enzymes. In many cases the exact mode of action or the targets are not known and synthesis of analogs provides a more detailed insight into the mode of action and helps to identify the protein target. We discuss the synthetic endeavors that led to the synthesis of members of the leptomycin family and will provide a picture of the mode of action.
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