874101-00-5

• 常用中文名：RO4987655
• 常用英文名：RO4987655
• CAS号：874101-00-5
• 分子式：C₂₀H₁₉F₃IN₃O₅
• 分子量：565.282
• 相关类别： 研究领域 癌症
• 发布时间：2016-10-16 16:02:44
• 更新时间：2025-08-28 22:07:23
• RO4987655 是一种具有口服活性的选择性 MEK 抑制剂,抑制 MEK1/MEK2,IC50 为 5.2 nM。

名称

• 中文名: RO4987655
• 英文名: 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide
• 英文别名: 3orn; Benzamide, 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-5-[(tetrahydro-3-oxo-2H-1,2-oxazin-2-yl)methyl]-; 3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]-N-(2-hydroxyethoxy)-5-[(3-oxo-1,2-oxazinan-2-yl)methyl]benzamide; RO4987655

物化性质

• 密度: 1.7±0.1 g/cm3
• 分子式: C₂₀H₁₉F₃IN₃O₅
• 分子量: 565.282
• 精确质量: 565.032166
• PSA: 103.62000
• LogP: 5.49
• 折射率: 1.638
• 储存条件: 2-8℃

生物活性

• 描述: RO4987655 是一种具有口服活性的选择性 MEK 抑制剂,抑制 MEK1/MEK2,IC50 为 5.2 nM。
• 相关类别:
  研究领域 >> 癌症
• 靶点:

  MEK1:5.2 nM (IC50)

  MEK2:5.2 nM (IC50)

• 体外研究: RO4987655有效抑制丝裂原活化蛋白激酶信号通路激活和肿瘤细胞生长,体外IC50为5.2 nM,可抑制MEK1/2 [1]。 RO4987655以剂量依赖性方式抑制NCI-H2122细胞的增殖,IC50值为0.0065μM。剂量范围为0.1至1.0μM的RO4987655在治疗开始后2小时已经抑制pERK1/2 [2]。
• 体内研究: 单剂口服施用RO4987655(CH4987655)导致异种移植模型中的完全肿瘤消退。 RO4987655快速吸收,tmax约为1小时。暴露的剂量比例为0.5至4毫克。配置是双相的,终端t1/2为~25小时。主体间变异性较低,Cmax为9％至23％,曲线下面积(AUC)为14％至25％。 pERK抑制是暴露依赖性的,并且在较高剂量下抑制大于80％。药代动力学-药效学关系的特点是使用非线性混合效应模型[1]抑制Emax模型(Emax~100％; IC50 40.6 ng/mL)。将雌性无胸腺裸鼠随机分入研究组。在第0天,第1天和第3天用1.0,2.5和5.0mg/kg RO4987655进行数字卡尺和PET扫描估计肿瘤大小。载体治疗在此时间范围内不抑制NCI-H2122肿瘤异种移植物生长。相比之下,RO4987655治疗在第3天导致1.1mg/kg的肿瘤生长抑制(TGI)为119％,2.5mg/kg时为145％TGI,5.0mg/kg时为150％TGI.PET成像显示[18F] FDG异种移植物的摄取在RO4987655给药后24小时(第1天)降低[2]。
• 细胞实验: 将人肺腺癌细胞系NCI-H2122维持在指定的培养基中，并指示热灭活的胎牛血清和L-谷氨酰胺的浓度。细胞在37℃，5％CO 2气氛中生长。将细胞用不同浓度的RO4987655（0.00001,0.001,0.1和10μM）在96孔板中处理72小时，并用细胞计数试剂盒-8定量活细胞[2]。
• 动物实验: 小鼠[2]使用雌性无胸腺裸鼠Balb nu / nu，年龄5至6周（18至22g）。将NCI-H2122细胞（4×106 /小鼠）皮下接种在Balb-nu / nu小鼠的右胁腹中。一旦建立肿瘤（100至200mm 3），将小鼠随机分组，在研究开始时具有相似的平均肿瘤体积。在第0天，第1天和第3天用1.0,2.5和5.0mg / kg RO4987655进行数字卡尺和PET扫描估计肿瘤大小。在[18 F] FDG-PET成像的第0天（基线），1,2,3和9测量肿瘤体积和体重。计算肿瘤生长抑制[2]。
• 参考文献:

  [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.

MSDS

SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: 3,4-Di-F-2-(2-F-4-I-Anilino)-N-(2-Ho-Eto)-5-[(3-Oxo- 2-Oxazinanyl)Me]Benzamide : MNO000162 REACH No.: A registration number is not available for this substance as the substance or its uses are exempted from registration, the annual tonnage does not require a registration or the registration is envisaged for a later registration deadline. SECTION 2: Hazards identification Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 Acute toxicity, Oral (Category 4), H302 For the full text of the H-Statements mentioned in this Section, see Section 16. Classification according to EU Directives 67/548/EEC or 1999/45/EC Xn HarmfulR22 For the full text of the R-phrases mentioned in this Section, see Section 16. Label elements Labelling according Regulation (EC) No 1272/2008 Pictogram Signal wordWarning Hazard statement(s) Harmful if swallowed. Precautionary statement(s)none Supplemental Hazardnone Statements Other hazards This substance/mixture contains no components considered to be either persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher. SECTION 3: Composition/information on ingredients Substances Molecular weight: 565,28 g/mol Hazardous ingredients according to Regulation (EC) No 1272/2008 ComponentClassificationConcentration 3,4-Di-F-2-(2-F-4-I-Anilino)-N-(2-Ho-Eto)-5-[(3-Oxo-2-Oxazinanyl)Me]Benzamide Acute Tox. 4; H302<= 100 % Hazardous ingredients according to Directive 1999/45/EC ComponentClassificationConcentration 3,4-Di-F-2-(2-F-4-I-Anilino)-N-(2-Ho-Eto)-5-[(3-Oxo-2-Oxazinanyl)Me]Benzamide Xn, R22<= 100 % For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16 SECTION 4: First aid measures Description of first aid measures General advice Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Consult a physician. In case of eye contact Flush eyes with water as a precaution. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician. Most important symptoms and effects, both acute and delayed The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in section 11 Indication of any immediate medical attention and special treatment needed No data available SECTION 5: Firefighting measures Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Nature of decomposition products not known. Advice for firefighters Wear self-contained breathing apparatus for firefighting if necessary. Further information No data available SECTION 6: Accidental release measures Personal precautions, protective equipment and emergency procedures Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Avoid breathing dust. For personal protection see section 8. Environmental precautions Do not let product enter drains. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. SECTION 7: Handling and storage Precautions for safe handling Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. For precautions see section 2.2. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Storage class (TRGS 510): Non Combustible Solids Specific end use(s) Apart from the uses mentioned in section 1.2 no other specific uses are stipulated SECTION 8: Exposure controls/personal protection Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Personal protective equipment Eye/face protection Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection Complete suit protecting against chemicals, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Control of environmental exposure Do not let product enter drains. SECTION 9: Physical and chemical properties Information on basic physical and chemical properties a) AppearanceForm: solid b) OdourNo data available c) Odour ThresholdNo data available d) pHNo data available e) Melting point/freezingNo data available point f) Initial boiling point and No data available boiling range g) Flash pointNo data available h) Evaporation rateNo data available i) Flammability (solid, gas) No data available j) Upper/lowerNo data available flammability or explosive limits k) Vapour pressureNo data available l) Vapour densityNo data available m) Relative densityNo data available n) Water solubilityNo data available o) Partition coefficient: n- No data available octanol/water p) Auto-ignitionNo data available temperature q) DecompositionNo data available temperature r) ViscosityNo data available s) Explosive propertiesNo data available t) Oxidizing propertiesNo data available Other safety information No data available SECTION 10: Stability and reactivity Reactivity No data available Chemical stability Stable under recommended storage conditions. Possibility of hazardous reactions No data available Conditions to avoid No data available Incompatible materials Strong oxidizing agents Hazardous decomposition products In the event of fire: see section 5 SECTION 11: Toxicological information Information on toxicological effects Acute toxicity No data available Skin corrosion/irritation No data available Serious eye damage/eye irritation No data available Respiratory or skin sensitisation No data available Germ cell mutagenicity No data available Carcinogenicity IARC:No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity No data available Specific target organ toxicity - single exposure No data available Specific target organ toxicity - repeated exposure No data available Aspiration hazard No data available Additional Information RTECS: Not available To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. SECTION 12: Ecological information Toxicity No data available Persistence and degradability No data available Bioaccumulative potential No data available Mobility in soil No data available Results of PBT and vPvB assessment This substance/mixture contains no components considered to be either persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher. Other adverse effects No data available SECTION 13: Disposal considerations Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging Dispose of as unused product. SECTION 14: Transport information UN number ADR/RID: -IMDG: -IATA: - UN proper shipping name ADR/RID: Not dangerous goods IMDG: Not dangerous goods IATA:Not dangerous goods Transport hazard class(es) ADR/RID: -IMDG: -IATA: - Packaging group ADR/RID: -IMDG: -IATA: - Environmental hazards ADR/RID: noIMDG Marine pollutant: noIATA: no Special precautions for user No data available SECTION 15: Regulatory information This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006. Safety, health and environmental regulations/legislation specific for the substance or mixture No data available Chemical Safety Assessment SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 海关编码: 2934999090

海关

海关编码	2934999090
中文概述	2934999090. 其他杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%