| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1558 | |
| Phytochemical name or plant extracts | 11,11'-dideoxyverticillin | |
| PMID | 15766573 | |
| Literature evidence | Together, these findings strongly suggest that 11,11'-dideoxyverticillin is a structurally novel angiogenesis inhibitor. | |
| IUPAC name | (1S,3R,11R,14S)-3-[(1S,3R,11R,14S)-14,18-dimethyl-13,17-dioxo-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-trien-3-yl]-14,18-dimethyl-15,16-dithia-10,12,18-triazapentacyclo[12.2.2.01,12.03,11.04,9]octadeca-4,6,8-triene-13,17-dione | |
| Phytochemicals’ class or type of plant extracts | Epidithiodioxopiprazine | |
| Source of phytochemicals or plant Extracts | Shiraia bambusicola | |
| Geographical availability | NA | |
| Plant parts | Fungi | |
| Other cancers | Breast cancer | |
| Target gene or protein | EGFR, VEGFR-1/Flt-1, HER2/ErbB-2, Erk1/2, Flt-1, KDR/Flk-1 | |
| Gene or Protein evidence | In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy-verticillin significantly inhibited the activities of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB-2), with relative specificity on EGFR and VEGFR-1 with IC50s of 0.136+/-0.109 and 1.645+/-0.885 nM, respectively. In addition, 11,11'-dideoxy-verticillin also inhibited the EGF-induced phosphorylation of Erk1/2, but had no effect on the phosphorylation of AKT in both tumor cell lines. In addition, 11,11'-dideoxyverticillin decreased VEGF secretion by MDA-MB-468 breast cancer cells, and significantly suppressed VEGF-induced tyrosine phosphorylation of Flt-1 and KDR/Flk-1. | |
| Target pathways | This inhibition of receptor phosphorylation was correlated with a marked decrease in VEGF-triggered pERK activation and a dramatic increase in pP38 MAPK, but no apparent change in pAkt. | |
| IC50 | 0.2 µM against MDA-MB-468 | |
| Potency | Together, these findings strongly suggest that 11,11'-dideoxyverticillin is a structurally novel angiogenesis inhibitor. These results indicate that 11,11'-dideoxy-verticillin is a naturally derived growth factor receptor tyrosine kinase inhibitor with potent anti-tumor activity. | |
| Cell line/ mice model | MDA-MB-468, HUVEC, Mice | |
| Additional information | Moreover, 11,11'-dideoxyverticillin completely blocked VEGF-induced microvessel sprouting from Matrigel-embedded rat aortic rings and vessel growth in Matrigel plugs in mice. Treated with 11,11'-dideoxy-verticillin at 0.5-2.0 microM for 36 h, MB-MB-468 cells exhibited significant apoptotic morphological changes. At low concentrations (0.0625-0.5 microM) for 24 h, 11,11'-dideoxy-verticillin induced a dose-dependent accumulation of MDA-MB-468 cells in the G2/M phase of the cell cycle. | |
| PubChem ID | 3084126 | |
| Additional PMIDs | 15846117 | |
| Additional sources of information | NA | |
| Safety | NA |