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In vitro: BI-847325 shows growth-inhibitory effects on BRAF-mutant and vemurafenib-resistant melanoma cells with IC50 ranging from 0.3 nM to 2 μM, and prevents colony formation in six BRAF-mutant melanoma cell lines. BI-847325 also induces apoptosis by reducing Mcl-1 expression. In vivo: In mice bearing 1205Lu and 1205LuR xenografts, BI-847325 (75 mg/kg, p.o.) causes significant tumor suppression without significant alteration in the body weights.
| Cell Experiment | |
|---|---|
| Cell lines | M229, M229R, A375, A375R, WM793, WM793R, 1205Lu, 1205LuR, M249, M249R, WM164, WM164R, WM39 and RPMI17951 cells |
| Preparation method | Cells are plated at a density of 2.5 × 10^3 cells per 100 μL and left to grow overnight before being treated with increasing concentrations of BI-847325 for 72 hours. The metabolic activity is determined using Alamar blue reagent as per the manufacturer's protocol. |
| Concentrations | 30 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | Mice bearing 1205Lu and 1205LuR xenografts |
| Formulation | 2-hydroxyethyl cellulose, polysorbate 80 with pH adjusted to 2.8 with 1 M HCl |
| Dosages | 70 mg/kg |
| Administration | p.o. |
| Molecular Weight | 464.56 |
| Formula | C29H28N4O2 |
| CAS Number | 1207293-36-4 |
| Solubility (25°C) | 19 mg/mL warmed in DMSO |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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