Potent Inhibitor of Human Trypsins from the Aeruginosin Family of Natural Products

著者: Muhammad N. Ahmed, Matti Wahlsten, Jouni Jokela, Matthias Nees, Ulf‐Håkan Stenman, Danillo Oliveira Alvarenga, Tomas Strandin, Kaarina Sivonen, Antti Poso, Perttu Permi, Mikko Metsä‐Ketelä, Hannu Koistinen, David P. Fewer - ACS Chemical Biology 2021 被引用: 30

of 104 nM. Molecular dynamics simulations suggested that suomilide has a long residence time when bound to trypsins. This was confirmed experimentally for trypsin-1 and -3 (residence times of 1.5 and 57 min, respectively). Suomilide also inhibited the invasion of aggressive and metastatic PC-3M prostate cancer cells without affecting cell proliferation. The potent inhibition of trypsin-3, together with a long residence time and the ability to inhibit prostate cancer cell invasion, makes suomilide an attractive drug lead for targeting cancers that overexpress trypsin-3. These results substantially broaden the genetic and chemical diversity of the aeruginosin family and suggest that aeruginosins may be a source of selective inhibitors of human serine proteases.