Novel targets are needed for treatment of devastating diseases such as cancer. Since decades, natural products are guiding innovative therapies by addressing diverse pathways. Inspired by the potent cytotoxic bioactivity of myxobacterial vioprolides A‐D we performed in depth studies on their mode of action. Based on the prominent potency against human acute lymphoblastic leukemia (ALL) cells we conducted thermal proteome profiling (TPP) and deciphered target proteins of the most active derivative vioprolide A (VioA) in Jurkat cells. Nucleolar protein 14 (NOP14), essential in ribosome biogenesis, was confirmed as specific target of VioA by a suite of proteomic and biological follow‐up experiments. Given its activity against ALL cells compared to healthy lymphocytes, VioA exhibits a unique therapeutic potential for anticancer targeting via an novel mode of action.
Kirsch, V.C.*, Orgler, C.*, Braig, S., Jeremias, I., Auerbach, D., Müller, R., Vollmar, A.M., Sieber, S.A., "The cytotoxic natural product vioprolide A target nucleolar protein 14 essential for ribosome biogenesis"
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