Herboxidiene (142861-00-5) is a novel polyketide fermentation product produced by Streptomyces chromofuscus, originally discovered by screening for herbicidal activity. Potent and selective inhibitor of spliceosome subunit SF3b.² Specifically targets SAP155, a subunit of SF3b responsible for pre-mRNA splicing.³ Displays anti-angiogenic activity via down-regulation of VEGFR-2 and HIF-1α.⁴ Spliceosome inhibitors have attracted enormous attention due to their potential use in cancer treatment.⁵

References/Citations

1) Miller-Wideman et al. (1992), Herboxidiene, a new herbicidal substance from Streptomyces chromofuscus A7847. Taxonomy, fermentation, isolation, physio-chemical and biological properties; J. Antibiot. (Tokyo), 45 914
2) Gao et al. (2013), Comparison of splicing factor 3b inhibitors in human cells; Chembiochem, 14 49
3) Hasegawa et al. (2011), Identification of SAP155 as the target of GEX1A (Herboxidiene), an antitumor natural product; ACS Chem. Biol., 6 229
4) Jung et al. (2015), Antiangiogenic activity of herboxidiene via downregulation of vascular endothelial growth factor receptor-2 and hypoxia-inducible factor-1α; Arch. Pharm. Res., 38 1728
5) Martinez-Montiel et al. (2016), Microbial and Natural Metabolites That Inhibit Splicing: A Powerful Alternative for Cancer Treatment; Biomed. Res. Int., epub ahead of print