| 產(chǎn)品描述： | RO4987655 is an orally active and highly selective MEK inhibitor (IC50: 5.2 nM for MEK1/MEK2). |
| 靶點： |
MEK |
| 體內(nèi)研究： |
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. 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) |
| 細胞實驗： |
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 |
| 動物實驗： |
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) |
| 參考文獻： |
1. Lee L, et al. The safety, tolerability, pharmacokinetics, and pharmacodynamics of single oral doses of CH4987655 in healthy volunteers: target suppression using a biomarker. Clin Cancer Res. 2009 Dec 1;15(23):7368-74. 2. Tegnebratt T, et al. Evaluation of efficacy of a new MEK inhibitor, RO4987655, in human tumor xenografts by [(18)F] FDG-PET imaging combined with proteomic approaches. EJNMMI Res. 2014 Dec;4(1):34. |
| 溶解性： |
Soluble in DMSO |
| 保存條件： |
RT |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.769 ml |
8.845 ml |
17.69 ml |
| 5 mM |
0.354 ml |
1.769 ml |
3.538 ml |
| 10 mM |
0.177 ml |
0.885 ml |
1.769 ml |
| 50 mM |
0.035 ml |
0.177 ml |
0.354 ml |
|
| 注意： |
部分產(chǎn)品我司僅能提供部分信息，我司不保證所提供信息的權(quán)威性，僅供客戶參考交流研究之用。 |
上海工商
危險品化學(xué)品經(jīng)營許可證（不帶存儲）
營業(yè)執(zhí)照(三證合一)
北京