81767-50-2Relevant academic research and scientific papers
Identification of a Covalent Importin-5 Inhibitor, Goyazensolide, from a Collective Synthesis of Furanoheliangolides
Barluenga, Sofia,Liu, Weilong,Loewith, Robbie,Patouret, Rémi,Plank, Michael,Winssinger, Nicolas
, p. 954 - 962 (2021)
Sesquiterpenes are a rich source of covalent inhibitors with a long history in traditional medicine and include several important therapeutics and tool compounds. Herein, we report the total synthesis of 16 sesquiterpene lactones via a build/couple/pair strategy, including goyasensolide. Using an alkyne-tagged cellular probe and proteomics analysis, we discovered that goyazensolide selectively targets the oncoprotein importin-5 (IPO5) for covalent engagement. We further demonstrate that goyazensolide inhibits the translocation of RASAL-2, a cargo of IPO5, into the nucleus and perturbs the binding between IPO5 and two specific viral nuclear localization sequences.
