product name FH535
Description: FH535 is a potent Wnt/β-catenin signaling inhibitor and also a dual PPARγ and PPARδ antagonist. FH535 can inhibit the growth of colon, lung, and hepatocellular carcinoma line but not normal fibroblasts. It makes FH535 potentially be a promising therapeutic approach for cancer cells. It is reported that FH535 has ability to inhibit growth, migration, and invasion of TN breast cancer cell lines (MDA-MB-231 and HCC38) without affecting adhesive abilities of cells to type I collagen.
References: Mol Cancer Ther. 2008;7(3):521-9; Int J Toxicol. 2012;31(4):380-9; PLoS One. 2014;9(6):e99272.
361.20
Formula
C13H10Cl2N2O4S
CAS No.
108409-83-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 72 mg/mL (199.3 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: FH535 antagonizes β-Catenin/Tcf–mediated transcription, and inhibits recruitment of the coactivators GRIP1 and β-catenin to PPARδ and PPARγ. FH535 shows selective anti-proliferation effect on some cancer cells expressing high or active Wnt/β-catenin pathway. FH535 increases cigarette smoke condensate cytotoxicity, and causes changes in β-catenin and EGR-1 signaling. FH535 has potential therapeutic value in treatment of liver cancer by targeting liver cancer stem cells and hepatocellular carcinoma cell lines. Kinase Assay: Three copies of the optimized or mutated Tcf-binding element from TOPFLASH or FOPFLASH driving a secreted alkaline phosphatase reporter gene are cloned into pCEP4 plasmid, replacing the cytomegalovirus promoter. The plasmids are transfected into HepG2 cells, and hygromycin-resistant clones are pooled. Library screening is done at 20 μmol/L concentration in HepG2 serum-free media. Hits are tested in the HCT116 cell line for inhibition of TOPFLASH luciferase activity but not for inhibition of a reporter activity controlled from β-actin promoter. Cell Assay: Cell viability is determined by the modified 3H-thymidine incorporation assay. Briefly, cells (HCT116, SW48, RKO, LoVo, COLO205, IEC6, A427, HCC15, NCI-H1703, A549, HepG2, Hep3b, Huh7, Fibroblasts) are plated in 96-well microplates for 24 h and treated in triplicate with various concentrations of the test compound. After 48 h of compound exposure, the cells are incubated for an additional 48 h in compound-free medium. The cells are then incubated in medium containing 3H-thymidine for 24 h, washed and mixed with the scintillant in the 96-well plate. Individual wells are counted with a 96-well scintillation counter and the LC50 is calculated. |
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| In Vivo | |
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| Formulation & Dosage | |
| References | Mol Cancer Ther. 2008 Mar;7(3):521-9. doi: 10.1158/1535-7163.MCT-07-2063; Int J Toxicol. 2012 Jul-Aug;31(4):380-9; PLoS One. 2014 Jun 18;9(6):e99272. |
