化合物RO4987655 T5412

Product Introduction
Bioactivity


英文名: RO4987655

描述: RO4987655 (RG7167) 是一种具有口服活性和高选择性的 MEK 抑制剂，抑制MEK1/MEK2，IC50为 5.2 nM。

细胞实验: Cells were treated with various concentrations of RO4987655 for 72 h in 96-well plates and viable cells were quantified with Cell Counting Kit-8. For Western blotting, cells were treated with RO4987655 for indicated periods and lysed with cell lysis buffer containing a protease inhibitor cocktail, phosphatase inhibitor cocktails 2 and 3, and 1 mM PMSF. For detection of protein bands, the following were used as primary antibodies: pEGFR, EGFR, pMKK4, MKK4, pAKT, AKT, pERK, ERK, pMEK1/2, MEK, Cyclin D1, and actin. All protein bands were visualized with secondary antibodies labeled with HRP and ECL system by using ImageQuant LAS 4000 [2].

动物实验: A time interval of 20 to 24 h was used between daily RO4987655 administration and completion of PET imaging for each tumor-bearing mouse and for each PET imaging time point (day 0, 1, 3 and 9). Mice were fasted for 6 to 8 h prior to start of the imaging session. [18F] FDG (7 to 8 MBq per mouse, maximum volume of 200 μL) was administered to awake, warmed (37°C) mice by a bolus injection via the tail vein. Forty to sixty minutes after the tracer injection, the mice were administered with isoflurane, controlled by an E-Z anesthesia vaporizer. The mice were placed on a heated pad (37°C) on the camera bed, with most of the body volume in the field of view (7.68 cm). Emission data were collected for 20 min in list mode with a microPET Focus 120 scanner. Maximum standardized uptake values (SUVmax) of [18F] FDG uptake in the tumor were calculated and normalized to the administered activity (MBq/body weight, g). The drug effect on tumor metabolism was estimated as%SUVmax change to day 0 (baseline) [2].

体外活性: CH4987655 (RO4987655) potently inhibits mitogen-activated protein kinase signaling pathway activation and tumor cell growth, with an in vitro IC50 of 5.2 nmol/L for inhibition of MEK1/2 [1]. In NCI-H2122 cells, RO4987655 at doses ranging from 0.1 to 1.0 μM suppressed pERK1/2 already at 2 h after the start of treatment. RO4987655 inhibited proliferation of NCI-H2122 cells in a dose-dependent manner with an IC50 value of 0.0065 μM [2].

体内活性: In the dose-ranging study, treatment with RO4987655 5.0 mg/kg led to dramatic decrease in FDG uptake on day 1. The daily RO4987655, 2.5 mg/kg treatment were followed by PET examinations on days 1, 3, and 9 of the drug administration. The maximum decrease was observed on day 1, followed by a slight rebound on day 3. The effect plateaued thereafter to day 9 of treatment [2]. Doses of 0.5, 1, 2, 3, and 4 mg were safe and well-tolerated. A total of 26 adverse events (n = 15) were reported: 21 mild, 5 moderate, and none severe. Moderate adverse events were experienced by one subject at 1 mg (autonomic nervous system imbalance) and three subjects at 4 mg (diarrhea, abdominal pain, autonomic nervous system, and acne) [3].

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 35 mg/mL (61.92 mM)


关键字: RG 7167 | CH 4987655 | RO 4987655 | MAPKK | RO4987655 | MEK | Mitogen-activated protein kinase kinase | MAP2K | RO-4987655 | Inhibitor | inhibit | RG-7167 | CH-4987655

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相关库: Drug Repurposing Compound Library | Anti-Cancer Compound Library | Anti-Cancer Drug Library | Kinase Inhibitor Library | Anti-Cancer Clinical Compound Library | Inhibitor Library | Anti-Colorectal Cancer Compound Library | Highly Selective Inhibitor Library | Anti-Cancer Active Compound Library | Bioactive Compound Library

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