SAR405_COA_24558_MedChemExpress
SAR405-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-09-2018Print Date:Oct.-09-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :SAR405Catalog No. :HY-12481CAS No. :1523406-39-41.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses :Laboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany:MedChemExpress USATel:609-228-6898Fax:609-228-5909E-mail:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Skin corrosion ⁄irritation (Category 2)Serious eye damage ⁄eye irritation (Category 2A)Specific target organ toxicity-single exposure(Category 3),Respiratory system2.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H315 Causes skin irritationH319 Causes serious eye irritationH335 May cause respiratory irritationPrecautionary statement(s)P261 Avoid breathing dust ⁄fume ⁄gas ⁄mist ⁄vapours ⁄spray.P305+351+338 IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do.Continue rinsing.P302+352 IF ON SKIN: wash with plenty of soap and water2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:SAR-405;SAR 405Formula:C19H21ClF3N5O2Molecular Weight:443.85CAS No. :1523406-39-44. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelids with fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT induce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE FIGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing apparatus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnel to safe areas.Refer to protective measures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas with appropriate exhaust ventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure controlsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance Off-white to light yellow (Solid)Odor No data availableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas)No data availableUpper/lower flammability or explosive limits No data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data availableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.Other decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious eye damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmed carcinogen by OSHA.Reproductive toxicityClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section 2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, federal, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
Cocktail探针药物法评价小檗碱对肝微粒体CYP450酶的抑制作用
Cocktail探针药物法评价小檗碱对肝微粒体CYP450酶的抑制作用目的：研究小檗碱对人肝微粒体CYP活性的影响。
方法：以苯海拉明为内标，建立LC-MS/MS同时测定5种探针药物：咪达唑仑、非那西丁、右美沙芬、甲苯磺丁脲和氯唑沙宗的含量，采用鸡尾酒（cocktail）法探针药物法评价不同浓度小檗碱对混合人肝微粒体CYP不同亚型活性的影响。
结果：与对照组相比，咪达唑仑、非那西丁和甲苯磺丁脲的代谢速率基本没有变化，而氯唑沙宗的代谢速率明显变慢，对于右美沙芬，当小檗碱的质量浓度为50 μg·L-1时，其代谢速率基本没有变化，当小檗碱的质量浓度大于200 μg·L-1时，其代谢速率明显变慢。
结论：小檗碱质量浓度在2 000 μg·L-1以下时对人肝微粒体中CYP3A4，CYP1A2和CYP2C9活性没有明显影响，但对CYP2E1和CYP2D6有明显的浓度依赖性抑制作用。
标签：鸡尾酒法；探针药物；混合人肝微粒体；小檗碱；P450酶抑制细胞色素P450酶（CYP）是肝微粒體混合功能氧化酶系的主要成分，是多种药物在体内代谢的最主要酶系[1]。
药物代谢与其体内浓度和药理活性密切相关，与此同时，药物也会对CYP产生诱导或抑制作用，从而引发药-药物相互作用和不良反应[2]。
复方是中药临床用药常见形式，配伍是中药的特色和优势，研究中药和CYP的关系，不但可以揭示药物的体内代谢过程，而且有助于了解药物间的相互作用与药效之间的内在联系，为组方配伍和临床合理用药提供直接依据[3]。
小檗碱，是中药黄连、黄柏等的主要有效成分，在临床上一直作为抗菌药和清热解毒药，随着研究不断深入，发现其具有抗高血压、抗肿瘤、降血糖等多方面的药理作用[4]。
目前研究表明小檗碱主要由小肠吸收，其口服吸收较差，生物利用度较低[5]，有关小檗碱的肝代谢酶表征及代谢产物的研究较清楚，小檗碱主要由CYP1A2和2D6代谢，代谢产物为小檗红碱和去亚甲基小檗碱及其葡萄糖醛酸苷共价结合物[6-7]。
GeXP简介
•Alignment
•Call scores
•Heterozygote Detection
2013/11/12
6
GeXP荧光系统
•GeXP更适合检测突变/杂合子： •波长越长，干扰越少 ，背景噪音低;
•650nm •laser •750nm •laser
•无10％的cut off把噪音，不会把10％以上杂合子去掉；
•NO Interference •from biological materials
7
个体化用药检测
KIT-Exon9
PDGFRA-exon12
EGFR突变检测
肿瘤药物对应相关基因的检测
药物名称 易瑞沙/特罗凯类 检测基因
EGFR-Exon18 突变 EGFR-Exon19 突变 EGFR-Exon21 突变 EGFR-Exon20突变 C-KIT-Exon9 突变 C-KIT-Exon11 突变 C-KIT-Exon13 突变 C-KIT-Exon17 突变 PDGFRα-Exon12 PDGFRα-Exon18 CYP2D6*10 多态性 XRCC1-Exon6 多态性 XRCC1-Exon10 多态性 ERCC1-codon118 多态性 MRP2-Exon10 多态性 BRCA1-Exon2 (女)多态性 BRCA1-Exon20 (女)多态性 XPD基因多态性 UGT1A1 *6 多态性 UGT1A1*28 多态性 DPYD*2A 多态性
伊马替尼 他莫昔芬
铂类
伊立替康 氟脲嘧啶类
HBV分型、耐药突变检测
2、片段分析
• 只需要研究长度，不需要知道具体序列 • 分别率为1bp
片段分析应用
STR/SSR
融合基因，可变剪切体
SAR405 _PI3K-Akt-mTOR_PI3K_CAS号1523406-39-4说明书_AbMole中国
和分子相互作用解释的。 SAR405抑制Vps34激酶活性影响晚期内体 - 溶酶体区室并防止自噬。 SAR405显示的结合平衡常数KD为1.52±0.77nM（±sd），解离速率
常数koff为3.03±0.55×10-3s-1，对应的停留半衰期t1 / 为2 3.8min 。接下来使用GFP-FYVE转染的HeLa细胞系在专门的Vps34细胞测定中评估SAR405的活性。
SAR405 目录号M7555
化学数据
分子量 分子式 号 CAS 储存条件
443.85 C19H21ClF3N5O2 1523406-39-4
3年 -20°C 粉末状
溶解性（25°C）
DMSO 27 mg/mL Water < 1 mg/mL Ethanol < 1 mg/mL
生物活性
SAR405是Vps34的低分子量激酶抑制剂（KD 1.5 nM）。 SAR405具有精细的蛋白质和脂质激酶选择性特征，这是由其在人Vps34的ATP结合裂隙内的独特结合模式
（IC 50 = 419nM）。还通过蛋白质印迹在野生型HeLa和H1299细胞上分析LC3-I到LC3-II的转化。
实验操作 来自于公开的文献，仅供参考
细胞实验
细胞系
RT-112 cells
一种国产胃泌素释放肽前体化学发光免疫试剂的性能验证
一种国产胃泌素释放肽前体化学发光 免疫试剂的性能验证
欧赛英１，徐海伟１，陈秀发１，沙利烽１，梁 辰２，冯 杰２，薛 辉２，颜光涛２
（１．苏州长光华医生物试剂有限公司，江苏 苏州 ２１５１６３； ２．中国人民解放军总医院医学检验中心，北京 １００８５３）
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ＯＵ Ｓａｉｙｉｎｇ１，ＸＵ Ｈａｉｗｅｉ１，ＣＨＥＮ Ｘｉｕｆａ１，ＳＡ Ｌｉｆｅｎｇ１，ＬＩＡＮＧ Ｃｈｅｎ２， ＦＥＮＧ Ｊｉｅ２，ＸＵＥＨｕｉ２，ＹＡＮ Ｇｕａｎｇｔａｏ２
（１．ＳｕｚｈｏｕＣｈａｎｇｇｕａｎｇｈｕａＭｅｄｉｃａｌＲｅａｇｅｎｔＣｏ．ＬＴＤ，Ｓｕｚｈｏｕ２１５１６３，Ｃｈｉｎａ； ２．ＭｅｄｉｃａｌＬａｂｏｒａｔｏｒｙＣｅｎｔｅｒｏｆＰＬＡ ＧｅｎｅｒａｌＨｏｓｐｉｔａｌ，Ｂｅｉｊｉｎｇ１００８５３，Ｃｈｉｎａ）
Ａｂｓｔｒａｃｔ：ＯｂｊｅｃｔｉｖｅＰｒｏＧＲＰｉｓａｐｒｏｍｉｓｉｎｇｅｆｆｅｃｔｉｖｅｔｕｍｏｒｍａｒｋｅｒｉｎｄｉｓｃｒｉｍｉｎａｔｉｎｇＳＣＬＣｆｒｏｍ ＮＳＣＬＣａｎｄ ｏｔｈｅｒｂｅｎｉｇｎｌｕｎｇｄｉｓｅａｓｅｓ．ＰｒｏＧＲＰＣｈｅｍｉｌｕｍｉｎｅｓｃｅｎｔｉｍｍｕｎｏａｓｓａｙ（ＣＬＩＡ）ｗａｓｄｅｖｅｌｏｐｅｄａｎｄｍａｎｕｆａｃｔｕｒｅｄ ｂｙＨｙｂｉｏｍｅ．Ｔｈｅｍａｎｕｆａｃｔｕｒｅｒｄｅｃｌａｒｅｄｔｈｅｐｅｒｆｏｒｍａｎｃｅｐａｒａｍｅｔｅｒｓａｓｆｏｌｌｏｗｉｎｇ：ｔｈｅｐｒｅｃｉｓｉｏｎｏｆｔｈｅｒｅａｇｅｎｔ ｗａｓｌｅｓｓｔｈａｎ１０％，ｔｈｅｌｉｍｉｔｏｆｄｅｔｅｃｔｉｏｎｗａｓ５ｐｇ／ｍＬ，ｔｈｅｒｅｃｏｖｅｒｙｗａｓｂｅｔｗｅｅｎ ＜±１０％，ｔｈｅｒｅｆｅｒｅｎｃｅ ｒａｎｇｅｗａｓ＜６５ｐｇ／ｍＬ，ｔｈｅｌｉｎｅａｒｒａｎｇｅｗａｓ１５３０００ｐｇ／ｍＬ，ｔｈｅｓｅｒｕｍ ｗａｓｗｅｌｌｃｏｒｒｅｌａｔｅｄｗｉｔｈｐｌａｓｍａ，ａｎｄ ｔｈｅｓｅｒｕｍ ｓｔａｂｉｌｉｔｙｃｏｕｌｄｒｅａｃｈ９６ｈｏｕｒｓ，ａｎｄｔｈｅｃｏｒｒｅｌａｔｉｏｎｗｉｔｈＲｏｃｈｅｅｌｅｃｔｒｏｃｈｅｍｉｌｕｍｉｎｅｓｃｅｎｃｅｐｒｏＧＲＰ ｒｅａｇｅｎｔｗａｓｇｏｏｄ．Ｔｈｅｐｅｒｆｏｒｍａｎｃｅｏｆｔｈｅｒｅａｇｅｎｔｗａｓｖｅｒｉｆｉｅｄｉｎｔｈｉｓｓｔｕｄｙ．ＭｅｔｈｏｄｓＡｃｃｏｒｄｉｎｇｔｏｔｈｅＣＬＳＩ ａｎｄＣＡＰ，ｔｈｅｐｒｅｃｉｓｉｏｎ，ｌｉｍｉｔｏｆｑｕａｎｔｉｔａｔｉｏｎ，ｒｅｃｏｖｅｒｙｒａｔｅ，ｌｉｎｅａｒｒａｎｇｅ，ｒｅｆｅｒｅｎｃｅｉｎｔｅｒｖａｌ，ｓｅｒｕｍ ｐｌａｓｍａ ｃｏｎｓｉｓｔｅｎｃｙ，ｓｅｒｕｍ ｓｔａｂｉｌｉｔｙａｎｄｃｏｍｐｌｅｍｅｎｔｉｎｔｅｒｆｅｒｅｎｃｅｏｆｔｈｅｄｏｍｅｓｔｉｃｐｒｏＧＲＰａｓｓａｙａｎｄｉｔｓｓｕｐｐｏｒｔｉｎｇ ｉｎｓｔｒｕｍｅｎｔ，ＡＥ１８０ｄｅｔｅｃｔｉｏｎｓｙｓｔｅｍ，ｗｅｒｅｖｅｒｉｆｉｅｄ．１９９ｃａｓｅｓａｍｐｌｅｓｆｒｏｍ ｈｅａｌｔｈｙｃｏｎｔｒｏｌ，ｓｍａｌｌｃｅｌｌｌｕｎｇ ｃａｎｃｅｒ，ｎｏｎｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒａｎｄｂｅｎｉｇｎｌｕｎｇｄｉｓｅａｓｅｐａｔｉｅｎｔｓ，ｗｅｒｅｄｅｔｅｃｔｅｄｉｎｐａｒａｌｌｅｌｗｉｔｈＲｏｃｈｅＥ６０１ ｓｙｓｔｅｍ ｔｏｃｏｍｐａｒｅｔｈｅｃｏｎｓｉｓｔｅｎｃｙｏｆｔｈｅｒｅｓｕｌｔｓｂｅｔｗｅｅｎｔｈｅｔｗｏｄｅｔｅｃｔｉｏｎｓｙｓｔｅｍｓ．ＲｅｓｕｌｔｓＴｈｅｎｅｗＰｒｏＧＲＰ
SAR405_ATP竞争性的Vps34抑制剂。_Apexbio
理工具用于研究该蛋白的生物学功能。由于 SAR405 独特的结合模式以及与人 Vps34 的 ATP 结合域的分子间相互作用，SAR405 具有蛋白和脂酶的选择性。SAR405 通过抑制 Vps34 激酶 活性，从而导致晚期内涵体-溶酶体积累并阻止自噬的发生。但是，SAR405 并不会影响早期 的内吞作用。同时，SAR405 会引起 cathepsin D 成熟的缺陷，表明溶酶体的功能受损。这与 早期的报道相一致：Vps34 siRNA 会影响从晚期内涵体到溶酶体的囊泡运输。 SAR405 抑制人重组 Vps34 对 PtdIns 的磷酸化，IC50 值为 1 nM。GFP-FYVE 的重定位表明 SAR405 抑制 PtdIns3P 的形成。SAR405 达到 10 μM 时对 I 型、II 型 PI3Ks 和 mTOR 均没有效果。在 PC3 细胞中，SAR405 浓度达到 10 μM 时并不影响 Akt 的磷酸化。SAR405（1 μM）可以与 来自 Jurkat 细胞裂解物的 Vps34 蛋白 ATP 结合位点以及脂酶相结合，其 KD 值是重组 Vps34 的 600 倍。
C[C@H]1N(C(N=C2N3CC[C@@H](C(F)(F)F)N2CC4=CN=CC(Cl)=C4)=C C3=O)CCOC1
>22.2mg/mL in DMSO
Store at -20°C
For obtaining a higher solubility , please warm the tube at 37°C and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months应时间 应用