| 名称 | Cobimetinib |
| 描述 | Cobimetinib (GDC-0973) is a MEK1 inhibitor (IC50=4.2 nM) with selective and oral activity. Cobimetinib exhibits antitumor activity, inhibiting tumor cell proliferation and inducing apoptosis. |
| 细胞实验 | Cells are plated in quadruplicate at a density of 3,000 per well in 384-well plates in normal growth medium and allowed to adhere overnight. Compounds are added in 10 concentrations based on a 3-fold dilution series. Cell viability is measured 72 h later using the CellTiter-Glo Luminescent Cell Viability Assay.(Only for Reference) |
| 体外活性 | METHODS: A panel of BRAF-mutant, RAS-mutant, or wild-type cell lines were treated with Cobimetinib for 96 h and cell viability was measured by Cell Death Detection ELISA Plus kit.
RESULTS: Cobimetinib showed potent cellular potency in multiple tumor types, particularly in BRAF or KRAS mutant cancer cell lines. In a subset of tumor cell lines, 80% of BRAF-mutant lines (both V600E and non-V600E mutations) were sensitive to Cobimetinib (EC50<1 µmol/L), 54% of lines harboring KRAS or NRAS-carrying mutations were sensitive, and the remaining 35% of lines were sensitive. [1]
METHODS: NB cell lines IMR-32, SHEP, and IMR-5 were treated with Cobimetinib (1 µM) for 4 h, and target protein expression levels were measured by Western Blot.
RESULTS: Cobimetinib treatment induced dephosphorylation of c-RAF and ERK and increased phosphorylation of MEK. [2] |
| 体内活性 | METHODS: To assay antitumor activity in vivo, Cobimetinib (1-10 mg/kg) was administered orally to mice bearing A375.X1 or NCI-H2122 xenografts once daily for 21 days.
RESULTS: In the A375.X1 BRAFV600E mutant melanoma xenograft model, treatment with a dose of Cobimetinib greater than 3 mg/kg resulted in an intense TGI, and in the NCI-H2122 KRASG12C mutant NSCLC xenograft model, treatment with up to 5 mg/kg Cobimetinib resulted in a moderate TGI, and treatment with 10 mg/kg approached tumor arrest. [1] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : 44 mg/mL (82.8 mM)
DMSO : 16.67 mg/mL (31.37 mM)
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| 关键字 | XL 518 | Apoptosis | RG-7420 | MEK | GDC0973 | Inhibitor | inhibit | MAP2K | MAPKK | Mitogen-activated protein kinase kinase | XL-518 | GDC 0973 | RG 7420 | Cobimetinib |
| 相关产品 | Stavudine | 5-Fluorouracil | Acetylcysteine | Myricetin | Sodium 4-phenylbutyrate | L-Ascorbic acid | Dextran sulfate sodium salt (MW 4500-5500) | Metronidazole | Sorafenib | Tributyrin |
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United States
