Talaverrucin A, Heterodimeric Oxaphenalenone from Antarctica Sponge-Derived Fungus <i>Talaromyces</i> sp. HDN151403, Inhibits Wnt/β-Catenin Signaling Pathway

Abstract

The Wnt/β-catenin signaling pathway is an evolutionarily conserved signaling cascade involved in a broad range of biological roles. Dysregulation of the Wnt/β-catenin pathway is implicated in congenital malformations and various kinds of cancers. We discovered a novel Wnt/β-catenin inhibitor, talaverrucin A (<b>1</b>), featuring an unprecedented 6/6/6/5/5/5/6 fused ring system, from an Antarctica sponge-derived fungus <i>Talaromyces</i> sp. HDN151403. Talaverrucin A exhibits inhibitory activity on the Wnt/β-catenin pathway in both zebrafish embryos <i>in vivo</i> and cultured mammalian cells <i>in vitro</i>, providing a naturally inspired small molecule therapeutic lead to target the Wnt/β-catenin pathway.