Yannick D Benoit, Ryan R Mitchell, Wenliang Wang, Luca Orlando, Allison L Boyd, Borko Tanasijevic, Lili Aslostovar, Zoya Shapovalova, Meaghan Doyle, Christopher J Bergin, Kinga Vojnits, Fanny L Casado, Justin Di Lu, Deanna P Porras, Juan Luis García-Rodriguez, Jennifer Russell, Aïcha Zouggar, Angelique N Masibag, Cody Caba, Kalinka Koteva, Lakshmana K Kinthada, Jagdish Suresh Patel, Sara N Andres, Jakob Magolan, Tony J Collins, Gerard D Wright, Mickie Bhatia
Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Biochemical and molecular studies revealed that McM025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in a variety of human cancers...
October 21, 2021: Cell Chemical Biology