694433-59-5

• 常用中文名：SB-505124
• 常用英文名：SB505124
• CAS号：694433-59-5
• 分子式：C₂₀H₂₁N₃O₂
• 分子量：335.400
• 相关类别： 生物化工 抑制剂 TGF-beta/Smad信号通路抑制剂(TGF-beta/Smad) TGF-beta/Smad 抑制剂
• 发布时间：2019-01-01 18:03:51
• 更新时间：2024-01-02 09:53:25
• SB-505124 是一种选择性的 TGFβR 抑制剂,对 ALK4,ALK5 的 IC50 值分别为 129 nM 和 47 nM。

名称

• 中文名: 2-(5-苯并[1,3]二氧代l-5-基-2-叔丁基-3H-咪唑-4-基)-6-甲基吡啶
• 英文名: 2-[4-(1,3-benzodioxol-5-yl)-2-tert-butyl-1H-imidazol-5-yl]-6-methylpyridine
• 中文别名: 2-[4-(1,3-苯并二氧杂环戊烷-5-基)-2-(1,1- 二甲基乙基)-1H-咪唑-5-基]-6-甲基-吡啶; 2-[4-(1,3-苯并二氧杂环戊烷-5-基)-2-(1,1-二甲基乙基)-1H-咪唑-5-基]-6-甲基-吡啶; 2-[4-(1,3-苯并二恶茂-5-基)-2-(叔丁基)-1H-咪唑-5-基]-6-甲基吡啶
• 英文别名: Pyridine, 2-[4-(1,3-benzodioxol-5-yl)-2-(1,1-dimethylethyl)-1H-imidazol-5-yl]-6-methyl-; 2-[4-(1,3-benzodioxol-5-yl)-2-tert-butyl-1H-imidazol-5-yl]-6-methylpyridine; SB 505124; 2-[4-(1,3-Benzodioxol-5-yl)-2-(2-methyl-2-propanyl)-1H-imidazol-5-yl]-6-methylpyridine; SB-505124; SB505124

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 509.7±50.0 °C at 760 mmHg
• 分子式: C₂₀H₂₁N₃O₂
• 分子量: 335.400
• 闪点: 180.5±20.4 °C
• 精确质量: 335.163391
• PSA: 60.03000
• LogP: 4.77
• 外观性状: yellow
• 蒸汽压: 0.0±1.3 mmHg at 25°C
• 折射率: 1.600
• 储存条件: 2-8°C
• 水溶解性: DMSO: >10mg/mL

生物活性

• 描述: SB-505124 是一种选择性的 TGFβR 抑制剂,对 ALK4,ALK5 的 IC50 值分别为 129 nM 和 47 nM。
• 相关类别:
  信号通路 >> TGF-beta/Smad 信号通路 >> TGF-β受体
  研究领域 >> 癌症
• 靶点:

  IC50: 129 nM (ALK4), 47 nM (ALK5)

• 体外研究: SB-505124证明在高达100μM的浓度下48小时对肾上皮A498细胞没有毒性。 505124抑制密切相关的ALK4,IC50值为129±11 nM(比ALK5敏感性低约2.5倍),但在高达10μM的浓度下不抑制ALK2。 SB-505124(1μM)以浓度依赖性方式抑制TGF-β诱导的所有这三种细胞系中Smad2的磷酸化。 SB-505124(1或5μM)有效抑制TGF-β诱导的JNK/SAP,细胞外信号调节激酶1/2和p38的激活,尽管这些细胞中的激活模式不同[1]。 SB-505124(10μM)在体外损害Smad2磷酸化和CTGF和α-SMA表达[2]。 SB-505124通过免疫荧光观察抑制CTGF和α-SMA。在GFS期间从施用SB-505124的眼睛切下的外植体中的细胞向外生长是稳健的,而用MMC处理的那些生长较差[3]。
• 激酶实验: 简而言之，磷酸-p38在4℃下用固定的磷-p38抗体从200μg细胞裂解物中免疫沉淀过夜。使用2μgATF-2融合蛋白作为底物并添加200μMATP来测量p38激酶活性。在30℃温育30分钟后，用LaemmLi样品缓冲液终止反应，将蛋白质煮沸并通过10％SDS-聚丙烯酰胺凝胶电泳分离，转移到硝酸纤维素膜上，并用磷酸-ATF-2抗体进行免疫印迹。 。
• 细胞实验: 如前所述或通过使用改良的四唑盐WST-1测量细胞活力。将大约2000个细胞接种在96孔培养皿中的100μL0.2％FBS无酚红培养基中过夜。将细胞用50μL的SB-505124（达到所示的最终浓度）处理30分钟，然后用或不用TGF-β1和TNF-α处理至终体积为200μL。通过在37℃下将每个孔与10μLWST-1孵育3小时，在指定的时间点测量细胞生长。代谢活性细胞将WST-1切割成水溶性甲,,其用酶联免疫吸附测定板读数器直接定量。每个实验至少进行两次，每个细胞系的处理一式三份进行。
• 参考文献:

  [1]. DaCosta Byfield S, et al. SB-505124 is a selective inhibitor of transforming growth factor-beta type I receptors ALK4, ALK5, and ALK7. Mol Pharmacol. 2004 Mar;65(3):744-52.

  [2]. Sutariya V, et al. Thermoreversible gel for delivery of activin receptor-like kinase 5 inhibitor SB-505124 for glaucoma filtration surgery. Pharm Dev Technol. 2013 Jul-Aug;18(4):957-62.

  [3]. Sapitro J, et al. Suppression of transforming growth factor-β effects in rabbit subconjunctival fibroblasts by activin receptor-like kinase 5 inhibitor. Mol Vis. 2010 Sep 16;16:1880-92.

MSDS

SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: SB-505124 hydrochloride hydrate 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. Relevant identified uses of the substance or mixture and uses advised against Identified uses: Laboratory chemicals, Manufacture of substances SECTION 2: Hazards identification Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 Skin irritation (Category 2), H315 Eye irritation (Category 2), H319 Specific target organ toxicity - single exposure (Category 3), Respiratory system, H335 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 Xi IrritantR36/37/38 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) H315Causes skin irritation. H319Causes serious eye irritation. H335May cause respiratory irritation. Precautionary statement(s) P261Avoid breathing dust. P305 + P351 + P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Supplemental Hazardnone Statements Other hazards - none SECTION 3: Composition/information on ingredients Substances Synonyms: 2-(5-Benzo[1,3]dioxol-5-yl-2-tert-butyl-3H-imidazol-4-yl)-6- methylpyridinehydrochloridehydrate Formula: C20H21N3O2 · xHCl · yH2O Molecular Weight: 335,40 g/mol Hazardous ingredients according to Regulation (EC) No 1272/2008 ComponentClassificationConcentration SB-505124 hydrochloride hydrate Skin Irrit. 2; Eye Irrit. 2; STOT <= 100 % SE 3; H315, H319, H335 Hazardous ingredients according to Directive 1999/45/EC ComponentClassificationConcentration SB-505124 hydrochloride hydrate Xi, R36/37/38<= 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 Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician. 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 Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas Advice for firefighters Wear self contained breathing apparatus for fire fighting 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. Evacuate personnel to safe areas. 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. Recommended storage temperature: 2 - 8 °C Store with desiccant. 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 impervious clothing, 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) Evapouration 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 Other decomposition products - no data available 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 Inhalation - May cause respiratory irritation. 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 PBT/vPvB assessment not available as chemical safety assessment not required/not conducted 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 For this product a chemical safety assessment was not carried out SECTION 16: Other information Full text of H-Statements referred to under sections 2 and 3. Eye Irrit.Eye irritation H315Causes skin irritation. H319Causes serious eye irritation. H335May cause respiratory irritation. Skin Irrit.Skin irritation STOT SESpecific target organ toxicity - single exposure Full text of R-phrases referred to under sections 2 and 3 XiIrritant R36/37/38Irritating to eyes, respiratory system and skin. Further information Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use only. The above information is believed to be correct but does not purport to be all inclusive and shall be used only as a guide. The information in this document is based on the present state of our knowledge and is applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee of the properties of the product. Corporation and its Affiliates shall not be held liable for any damage resulting from handling or from contact with the above product. See and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

安全

• 危害码 (欧洲): Xi
• 风险声明 (欧洲): 36/37/38
• 安全声明 (欧洲): 26-36
• 海关编码: 29349990