The downstream effectors of the Hippo pathway, the YAP/TAZ-TEAD transcription factor complexes, are attractive therapeutic targets in oncology that are hyperactivated in many different types of cancers and associated with poor prognosis. In this paper, Hillen, Candi, et al. present a novel TEAD inhibitor, SWTX-143, that binds to the palmitoylation pocket of all four TEAD isoforms and efficiently blocks Hippo pathway output in vitro and in vivo. SWTX-143 treatment was well tolerated in mice and induced tumor regression in xenograft and Lats1/2;p53 mutant mouse models for mesothelioma, a devastating cancer that is frequently driven by mutations in Hippo pathway components.

Geranylgeranyl diphosphate synthase (GGDPS), an enzyme in the isoprenoid biosynthetic pathway, has garnered interest as a potential therapeutic target in cancer. GGDPS inhibitor development has primarily focused on optimizing the interactions between the inhibitors (typically nitrogen-containing bisphosphonate agents) and the target enzyme. Still, a detailed understanding of the enzyme structure...

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