product name CCT007093
Description: CCT007093, a thienylidene cyclopentanone, is a potent PPM1D (WIP1) inhibitor with IC50 of 8.4 μM. CCT007093 shows a potent inhibition of PPM1D in the in vitro assay when using the recombinant phospho-P38 as a substrate. In cellular assay, CCT007093 shows specificity for MCF-7 cells over HeLa cells. It reduces 40% viability of the cells after 2 days. It is found that the cell death induced by CCT007093 is dependent on P38 kinase activity. CCT007093 mimics the effect of PPM1D RNAi in activating P38 kinase.
References: Oncogene. 2008;27(8):1036-44; Breast Cancer Res. 2010;12(3):R41; J Dermatol Sci. 2014;73(2):125-34.
272.39
Formula
C15H12OS2
CAS No.
176957-55-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: <1 mg/mL
Water: <1 mg/mL
DMF: 3 mg/mL (11.0 mM)
Solubility (In vivo)
5% DMSO+Corn oil: 1 mg/mL warmed (3.67 mM)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: CCT007093 selectively and potently inhibits human tumor cell lines (MCF-7, KPL-1, and MCF-3B) that overexpress PPM1D. CCT007093 induces cell death via the activation of p38 kinase activity. CCT007093 in combination with paclitaxel, results in synergistic inhibition of the four paclitaxel-resistant triple-negative breast cancer (TNBC) cell lines. CCT007093 selectively promote apoptosis in breast cancer cells and skin transformed keratinocytes that ectopically expressed Wip1, while attenuates the UV-mediated apoptotic response in both skin keratinocytes and a Wip1-null cell model. Kinase Assay: Recombinant PPM1D (20-50 pmol) is diluted in Tris buffer (50 mM, pH 8), NaCl (100 mM), β-mercaptoethanol (1 mM) or DTT (1 mM) and treated with MnCl2 (0, 1, 10 and 20 mM) or MgCl2 (0 and 40 mM). Where appropriate, inhibitors of PPM1D (10-50 μM) are added and the assay mix incubated for 30 min at room temperature. Recombinant phospho-P38 (200 pmol) is then added and the mixture incubated at 37°C for 1 h. The reaction is quenched by the addition of excess ethylenediaminetetraacetic acid (EDTA), sodium dodecyl sulphate-sample loading buffer and boiling for 5 min at 95°C followed by gel electrophoresis and western blotting. Cell Assay: Cells (MCF-7, KPL-1, and MCF-3B cells) are transfected with a pSUPER plasmid and an additional plasmid expressing the blasticidin resistance gene (pEFBsd) in a molar ratio of 10:1. Cells are plated in 10 cm plates 24 h after transfection. Blasticidin selection (5 μg/ml) is initiated 48 h post-transfection and replenished every 3 days. Colonies are fixed in methanol and stained with crystal violet after 14 days. Colonies are quantified on a Colcount and the surviving fraction (SF) determined. |
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| In Vivo | |
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| Formulation & Dosage | |
| References | Oncogene. 2008 Feb 14;27(8):1036-44; Breast Cancer Res. 2010;12(3):R41; J Dermatol Sci. 2014 Feb;73(2):125-34. |
