| Properties | Information | |
|---|---|---|
| PhytoCAT-ID | PhytoCAT-1140 | |
| Phytochemical name or plant extracts | Dihydro-β-agarofuran | |
| PMID | 15466210 | |
| Literature evidence | Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1, MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein, BCRP) transporters. | |
| IUPAC name | (1S,2R,6S,9R)-2,6,10,10-tetramethyl-11-oxatricyclo[7.2.1.01,6]dodecane | |
| Phytochemicals’ class or type of plant extracts | Sesquiterpenes | |
| Source of phytochemicals or plant Extracts | Maytenus cuzcoina, Maytenus canariensis, Maytenus magellanica, Maytenus chubutensis | |
| Geographical availability | Argentina South, Chile Central, Chile South | |
| Plant parts | NA | |
| Other cancers | Breast cancer | |
| Target gene or protein | P-gp | |
| Gene or Protein evidence | Sesquiterpenes from Celastraceae are promising P-glycoprotein modulators with potential applications in cancer chemotherapy because of their MDR reversal potency and specificity for P-glycoprotein. | |
| Target pathways | NA | |
| IC50 | NA | |
| Potency | Cytotoxicity assays using human MDR1-transfected NIH-3T3 cells allowed us to select the most potent sesquiterpenes reversing the in vitro resistance to daunomycin and vinblastine. Flow cytometry experiments showed that the above active compounds specifically inhibited drug transport activity of P-glycoprotein in a saturable, concentration-dependent manner (K(i) down to 0.24 +/- 0.01 micromol/L) but not that of ABCC1 (multidrug resistance protein 1, MRP1), ABCC2 (MRP2), and ABCG2 (breast cancer resistance protein, BCRP) transporters. Moreover, sesquiterpenes inhibited at submicromolar concentrations the P-glycoprotein-mediated transport of [(3)H]colchicine and tetramethylrosamine in plasma membrane from CH(R)B30 cells and P-glycoprotein-enriched proteoliposomes, supporting that P-glycoprotein is their molecular target. | |
| Cell line/ mice model | MDA-MB-231, NIH-3T3, NIH-3T3 MDR-G185, MDCKII, MDCKII-MRP2,MDA-MB-231-BCRP | |
| Additional information | Finally, sesquiterpenes modulated P-glycoprotein ATPase-activity in a biphasic, concentration-dependent manner: they stimulated at very low concentrations but inhibited ATPase activity as noncompetitive inhibitors at higher concentrations. | |
| PubChem ID | 21593552 | |
| Additional PMIDs | NA | |
| Additional sources of information | https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:155482-2 | |
| Safety | NA |