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ZM 336372 is a potent, selective ATP-competitive inhibitor of c-Raf in vitro (IC50 = 70 nM for inhibition of human c-Raf). The Ras/Raf-1 signalling pathway is a well-characterized system that links receptor tyrosine kinase (RTK) activation with changes in gene expression and cell behavior. Raf-1 is a serine/threonine protein kinase that phosphorylates and activates MAPK-kinase (MEK) in response to activation by Ras. ZM 336372 also inhibits SAPK2/p38 (IC50 = 2 μM). Selective over 17 other protein kinases including PKA, PKC, p42 MAPK, CDK1 and SAPK1/JNK (up to 50 μM). ZM 336372 causes growth inhibition, suppression of hormone secretion, and up-regulation of cell cycle inhibitors in a human hepatocellular carcinoma cell line.
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Source | J Surg Res (2010). Figure 1. ZM 336372 |
| Method | MTT assay | |
| Cell Lines | pancreatic adenocarcinoma cells | |
| Concentrations | 100 μM | |
| Incubation Time | 8 d | |
| Results | Here we utilize the MTT assay to determine if there is a difference in cellular proliferation in response to treatment with ZM336372 in pancreatic adenocarcinoma cells |
| Cell Experiment | |
|---|---|
| Cell lines | H727 and BON cells |
| Preparation method | Cell Proliferation Assay Proliferation of H727 and BON cells after treatment with ZM336372 was measured using a 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Cells were trypsinized and plated in triplicate to 24-well plates and allowed to adhere overnight. Then, cells were treated with either 100 μmol/L ZM336372 or DMSO (2%) and incubated. Media were changed every 2 days with new treatment. At each time point, cell growth rates were analyzed after the addition of 3,4-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reagent to the cultured cells following manufacturer's instructions. Absorbance was determined using spectrophotometer at a wavelength of 540 nm. |
| Concentrations | 100 μmol/L |
| Incubation time | 10 days |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 389.45 |
| Formula | C23H23N3O3 |
| CAS Number | 208260-29-1 |
| Solubility (25°C) | DMSO 50 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[3] Hall-Jackson CA, et al. Chem Biol. Paradoxical activation of Raf by a novel Raf inhibitor.
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