Decernotinib_DataSheet_MedChemExpress

Intended Use:For In Vitro Diagnostic UseHeat induced antigen retrieval of formalin-fixed paraffin-embedded (FFPE) tissues for immunohistochemistry (IHC) procedures. The clinical interpretation of any staining or its absence should be complimented by morphological studies using proper controls and should be evaluated within the context of the patient's clinical history and other diagnostic tests by a qualified pathologist.Summary & Explanation:Diva Decloaker is a heat retrieval solution that is compatible with virtually all antibodies and eliminates the need for multiple buffers including citrate buffer, EDTA or high pH tris buffers. Antibody titers are doubled and tripled when compared to citrate buffer, pH 6.0. Diva Decloaker incorporates Assure™ tech nology, a color-coded high temperatures pH indicator solution. The end-user is assured by visual inspection that the solution is at the correct dilution and pH. This product is specially formulated for superior pH stability at high temperatures and will help prevent the possibility of losing pH sensitive antigens. Diva Decloaker is non-toxic, non-flammable, odorless and sodium azide and thimerosal free.Known Applications:Immunohistochemistry (formalin-fixed paraffin-embedded tissues) Supplied As:100mlDiva Decloaker, 10X concentrate (DV2004LX)500mlDiva Decloaker, 10X concentrate (DV2004MX)Materials and Reagents (Needed But Not Provided): Microscope slides, positively chargedDesert Chamber* (Drying oven)Positive and negative tissue controlsXylene (Could be substituted with xylene substitute*)Ethanol or reagent alcoholDecloaking Chamber* (Pressure cooker)Deionized or distilled waterWash buffer*(TBS/PBS)Enzyme digestion*Avidin-Biotin Blocking Kit*(Labeled Streptavidin Kits Only) Peroxidase block*Protein block*Primary antibody*Negative control reagents*Detection kits*Detection components*Chromogens*Hematoxylin*Bluing reagent*Mounting medium** Biocare Medical Products: Refer to a Biocare Medical catalog for further information regarding catalog number and ordering information. Certain reagents listed above are based on specific application and detection system used. Storage and Stability:Store at room temperature. Do not use after expiration date printed on vial. If reagents are stored under conditions other than those specified in the package insert, they must be verified by the user. Diluted reagents should be used promptly; any remaining reagent should be stored at room temperature.Protocol Recommendations:1. Deparaffinize tissues and hydrate to water. If necessary, block for endogenous peroxidase and wash in DI water.2. Dilute concentrated Diva Decloaker at a ratio of 1:10 (1 ml Diva to 9 ml of deionized water).3. Place slides into 1X retrieval solution in a slide container (e.g. Coplin Jar, Tissue -Tek™ staining dish or metal slide canister).4. Retrieve sections under pressure using Biocare's Decloaking Chamber. Follow the recommendations on the antibody data sheet and Decloaking Chamber User Manual.5. Check solution for appropriate color change. (See Technical Note #1)6. Gently rinse by gradually adding DI water to the solution, then remove slides and rinse with DI water.Technical Notes:1. Concentrated Diva Decloaker is a bright yellow color. RTU or 1X solution is a pale yellow color. When the solution reaches 80-125°C, the solution turns yellow and indicates that the high temperature solution is at correct pH. Should the pH rise above 7.0, the solution turns a fuschia red color. Should the pH drop too low, thesolution turns a pink color.2. If using Biocare’s Desert Chamber Pro (a programmable turbo-action drying oven), dry sections at 25ºC overnight or at 37ºC for 30-60 minutes and then dry slides at 60ºC for 30 minutes.3. Use positive char ged slides (use Biocare’s Kling-On HIER Slides) and cut tissues at 4-5 microns. Do not use any adhesives in the water bath. Poor fixation and processing of tissues will cause tissue sections to fall off the slides, especially fatty tissues such as breast. Tissues should be fixed a minimum of 6-12 hours.4. Protocol time and temperatures for HIER can vary depending on the Decloaking Chamber model used. Please refer to the relevant Decloaking Chamber manual for appropriate protocol times and temperatures.Limitations:The protocols for a specific application can vary. These include, but are not limited to: fixation, heat-retrieval method, incubation times, tissue section thickness and detection kit used. Due to the superior sensitivity of these unique reagents, the recommended incubation times and titers listed are not applicable to other detection systems, asresults may vary. The data sheet recommendations and protocols are based on exclusive use of Biocare products. Ultimately, it is the responsibility of the investigator to determine optimal conditions. The clinical interpretation of any positive or negative staining should be evaluated within the context of clinical presentation, morphology and other histopathological criteria by a qualified pathologist. The clinical interpretation of any positive or negative staining should be complemented by morphological studies using proper positive and negative internal and external controls as well as other diagnostic tests.Catalog Number: DV2004 LX, MX Description: 100, 500 ml, concentrateQuality Control:Refer to CLSI Quality Standards for Design and Implementation of Immunohistochemistry Assays; Approved Guideline-Second edition (I/LA28-A2). CLSI Wayne, PA, USA (). 2011 Precautions:1. This product is not classified as hazardous. The preservative used in this reagent is Proclin 300 and the concentration is less than 0.25%. Overexposure to Proclin 300 can cause skin and eye irritation and irritation to mucous membranes and upper respiratory tract. The concentration of Proclin 300 in this product does not meet the OSHA criteria for a hazardous substance. Wear disposable gloves when handling reagents.2. Specimens, before and after fixation, and all materials exposed to them should be handled as if capable of transmitting infection and disposed of with proper precautions. Never pipette reagents by mouth and avoid contacting the skin and mucous membranes with reagents and specimens. If reagents or specimens come in contact with sensitive areas, wash with copious amounts of water.3. Microbial contamination of reagents may result in an increase in nonspecific staining.4. Incubation times or temperatures other than those specified may give erroneous results. The user must validate any such change.5. Do not use reagent after the expiration date printed on the vial.6. The SDS is available upon request and is located at /.7. Consult OSHA, federal, state or local regulations for disposal of any toxic substances. Proclin is a trademark of Rohm and Haas Company, or of its subsidiaries or affiliates.Troubleshooting:Follow the antibody specific protocol recommendations according to data sheet provided. If atypical results occur, contact Biocare's Technical Support at 1-800-542-2002.。

核准日期：2011年12月31日修改日期：2014年02月18日2014年10月31日2016年01月12日2017年01月16日2018年04月28日2018年11月08日2018年11月21日2020年04月07日2020年06月24日2021年XX月XX日雷珠单抗注射液说明书请仔细阅读说明书并在医师指导下使用。

【药品名称】通用名称：雷珠单抗注射液商品名称：诺适得®/Lucentis®英文名称：Ranibizumab Injections汉语拼音：Leizhu Dankang Zhusheye【成份】活性成份：雷珠单抗化学名称：G1，抗-（人血管内皮生长因子）Fab片断（人-鼠单克隆rhuFabV2γ1-链），二硫键结合人-鼠单克隆rhuFabV2κ-链分子量：48KD处方组成：1mL含10mg雷珠单抗。

本品所含辅料为：α,α-海藻糖二水合物；组氨酸；盐酸组氨酸一水合物；聚山梨醇酯20。

【性状】透明至微乳白色液体。

【适应症】雷珠单抗注射液适用于成人:∙用于治疗湿性（新生血管性）年龄相关性黄斑变性（AMD）。

∙用于治疗糖尿病性黄斑水肿（DME）引起的视力损害。

∙用于治疗糖尿病视网膜病变（DR）[增殖性糖尿病视网膜病变（PDR）和中重度至重度非增殖性糖尿病视网膜病变（NPDR）]。

∙用于治疗继发于视网膜静脉阻塞（RVO）（视网膜分支静脉阻塞（BRVO）或视网膜中央静脉阻塞（CRVO））的黄斑水肿引起的视力损害。

∙用于治疗脉络膜新生血管（CNV，即继发于病理性近视（PM）和其它原因的CNV）导致的视力损害。

雷珠单抗注射液适用于早产儿:∙用于治疗I区（1+、2+、3或3+期）、II区（3+期）早产儿视网膜病变（ROP）和AP-ROP（急进性后极部ROP）。

【规格】10mg/mL，每瓶装量0.20mL。

【用法用量】本品应在有资质的医院和眼科医生中使用。

医院应具备疾病诊断和治疗所需的相关仪器设备和条件，眼科医生应具备确诊湿性年龄相关性黄斑变性，糖尿病性黄斑水肿，糖尿病视网膜病变（DR）[增殖性糖尿病视网膜病变（PDR）和中重度至重度非增殖性糖尿病视网膜病变（NPDR）],继发于视网膜静脉阻塞（RVO）的黄斑水肿，脉络膜新生血管疾病以及早产儿视网膜病变的能力和丰富的玻璃体内注射经验。

Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :EnsartinibCatalog No. :HY-16590CAS No. :1365267-27-11.2 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 mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:X⁻396; X 396; X396Formula:C25H25Cl2FN6O3Molecular Weight:547.41CAS No. :1365267-27-14. 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 White to off-white (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 2017 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。

MSDS1 Composition7 Accident Release MeasureProduct Name:LinsitinibChemical Name:PROCEDURE(S) OF PERSONAL PRECAUTION(S)-Wear respirator, chemical safety goggles, rubber boots, and heavyrubber gloves.METHODS FOR CLEANING UP-Sweep up, place in a bag and hold for waste disposal. Avoid raising dust. Ventilate area andwash spill site after material pickup is complete.Cyclobutanol, 3-[8-amino-1-(2-phenyl-7-quinolinyl)imidazo[1,5-a]pyrazin-3-yl]-1-methyl-, cis-CAS No.:867160-71-28 Accident Release MeasureAppearance:light yellow to yellow(Solid)Formula:C26H23N5O9 Toxicological InformationSolubility:To the best of our knowledge, the chemical, physical, andtoxicological properties have not been thoroughly investigated.No data available.p p p p DMSO ≥81mg/mL Water <1.2mg/mLEthanol <1.2mg/mL2 Handling and Storage10 Regulary Information3 Stability and Reactivity11Disposal ConsiderationsCLASSIFICATION- Substance not yet fully tested.SAFETY PHASES- 26-36 (In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Wear suitable protective clothing.) 36/37/38 (Irritating to eyes,respiratory system and skin.)STABILITY- Stable under normal handling conditions.HANDLING- Do not breathe dust. Avoid contact with eyes,skin,and clothing.Avoid prolonged or repeated exposure.STORAGE- Store in a properly sealed container store at -20℃,shelflife is 2 years.11 Disposal Considerations 4 Hazards Identification12 Transport Information5First Aid RID/ADR- Non-hazardous for road transport. IMDG- Non-hazardous for sea transport.IATA - Non-hazardous for air transport.As specific country, federal, state and local environmentalregulations vary and change frequently we suggest you contact a local, authorized waste disposal contractor for adequate disposal.Special indication of hazards to humans and the environment.Irritating to eyes, respiratory system and skin.MATERIALS TO AVOID- Strong oxidizing agents.REACTIVITY- May emit toxic gasses like Carbon monoxide,Carbon dioxide, Nitrogen oxides upon thermal decomposition.5 First Aid13 Other InformationThe 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. Medchemexpress LLC shall not be held liable for any damage resulting from h dli f t t ith th b d tINHALATION- If inhaled, remove to fresh air. If not breathing give, artificial respiration. If breathing is difficult, give oxygen.SKIN CONTACT- In case of contact, immediately wash skin withsoap and copious amounts of water.EYE CONTACT- In case of contact, immediately flush eyes withcopious amounts of water for at least 15 minutes.INGESTION- If swallowed, wash out mouth with water provided person is conscious. Call a physician.6 Fire Fighting Measureshandling or from contact with the above product.EXTINGUISHING MEDIA Water spray- Carbon dioxide, dry chemical powder, or appropriate foam.SPECIAL RISKS Specific Hazard(s)- Emits toxic fumes under fire conditions. SPECIAL PROTECTIVE EQUIPMENT FOR FIREFIGHTERS Wear self-contained breathing apparatus and protective clothing Caution: Not fully tested. For research purposes onlyMedchemexpress LLCto prevent contact with skin and eyes.18 W i l k i n s o n W a y , P r i n c e t o n , N J 08540,U S AE m a i l : i n f o @m e d c h e m e x p r e s s .c o m W e b : w w w .m e d c h e m e x p r e s s .c o m。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:b–AP15 is a specific inhibitor of the deubiquitinating enzymes UCHL5 and Usp14.IC50 & Target: UCHL5/Usp14[1]In Vitro: Purified 19S proteasomes (5 nM) are treated with indicated concentrations of b–AP15 and DUB activity is determined by detectionof Ub–AMC cleavage. The IC 50 value (2.1±0.411 μM) is determined from log concentration curves in Graph Pad Prism using non linear regression analysis. b–AP15 as a previously unidentified class of proteasome inhibitor that abrogates thedeubiquitinating activity of the 19S regulatory particle. b–AP15 inhibited the activity of two 19S regulatory–particle–associated deubiquitinases, ubiquitin C–terminal hydrolase 5 (UCHL5) and ubiquitin–specific peptidase 14 (USP14), resulting in accumulation of polyubiquitin. b–AP15 induced tumor cell apoptosis that is insensitive to TP53 status and overexpression of the apoptosisinhibitor BCL2[1]. The ability of b–AP15 is determined to inhibit proteasome deubiquitinase activity using Ub–AMC as the substrate.An IC 50 of 16.8±2.8 μM is observed [2]. b–AP15 is a specific USP14 and UCHL5 inhibitor, which blocks growth and induces apoptosis in MM cells [3].In Vivo: b–AP15 (2.5 mg/kg) inhibits tumor growth in syngenic mice models with less frequent administration schedules. We administered b–AP15 to C57BL/6J mice with Lewis lung carcinomas (LLCs) using a 2–d–on, 2–d–off schedule and to BALB/c mice with orthotopic breast carcinoma (4T1) using a 1–d–on, 3–d–off schedule. b–AP15 significantly inhibited tumor growth in both models, with T/C=0.16 (P≤0.01) for the C57BL/6J mice and T/C=0.25 (P≤0.001) for the BALB/c mice. A reduction in the number of pulmonary metastases also is observed in the group of mice with 4T1 breast carcinomas treated with b–AP15[1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]For deubiquitinase inhibition assays, 19S regulatory particle (5 nM), 26S (5 nM) UCH–L1 (5 nM), UCH–L3 (0.3 nM),USP2CD (5 nM) USP7CD (5 nM) USP8CD (5 nM) or BAP1 (5 nM) is incubated with DMSO or b–AP15 and monitored the cleavage of ubiquitin–AMC (1,000 nM) using a Wallac VICTOR Multilabel counter or a Tecan Infinite M1000 equipped with 380 nm excitation and 460 nm emission filters [1].Cell Assay: b–AP15 is dissolved in DMSO and stored, and then diluted with appropriate medium before use [2]. [2]Cell viability is monitored by either the fluorometric microculture cytotoxicity assay or the MTT assay. For the MTT assay, cells are seeded into 96–well flat–bottomed plates overnight and exposed to drugs, using DMSO as the control. At the end of incubations, 10 μl of a stock solution of 5 mg/mL MTT is added into each well, and the plates are incubated 4 hours at 37°C. Formazan crystals are dissolved with 100 μL 10% SDS/10 mM HCl solution overnight at 37°C. Absorbance is measured using an enzyme–linkedimmunosorbent assay (ELISA) plate reader at 590 nm [2].Animal Administration: b–AP15 is dissolved it in Cremophor EL and polyethylene glycol 400 (1:1) by heating to reach aworking concentration of 2 mg/mL. Working stock is 1:10 diluted in 0.9% saline immediately before injection (Mice)[1].[1]Mice [1]For the squamous carcinoma model, 1×106 FaDu cells are subcutaneously injected into the right rear flank of female SCIDProduct Name:b–AP15Cat. No.:HY-13989CAS No.:1009817-63-3Molecular Formula:C 22H 17N 3O 6Molecular Weight:419.39Target:Deubiquitinase Pathway:Cell Cycle/DNA Damage Solubility:DMSO: ≥ 44 mg/mLmice. Tumor growth is measured by the formula length×width2×0.44. When tumors have grown to a size of approximately 200 mm3 (defined as day 0), mice are randomized to receive either vehicle (n=10) or b–AP15 (n=15) at 5 mg per kg of body weight by daily subcutaneous injection. For the colon carcinoma model, we subcutaneously injected 2.5 × 106 HCT–116 colon carcinoma cells overexpressing Bcl2 into the right flank of female nude mice. We treated mice with 5 mg of b–AP15 per kg of body weight by intraperitoneal injection. For the lung carcinoma model, we subcutaneously injected 2×105 LLC cells into the right rear flank of female C57/B6 mice. When tumors had grown to a size of approximately 50 mm3 (defined as day 0), we randomized mice to receive either vehicle (n=4) or b–AP15 (n=4) at 5 mg per kg of body weight intraperitoneally, with a treatment cycle consisting of 2 d of treatment followed by 2 d of rest (2 d on, 2 d off) for 2 weeks.References:[1]. D'Arcy P, et al. Inhibition of proteasome deubiquitinating activity as a new cancer therapy. Nat Med. 2011 Nov 6;17(12):1636–40.[2]. Wang X, et al. The 19S Deubiquitinase Inhibitor b–AP15 is Enriched in Cells and Elicits Rapid Commitment to Cell Death. Mol Pharmacol. 2014 Jun;85(6):932–45.[3]. Tian Z, et al. A novel small molecule inhibitor of deubiquitylating enzyme USP14 and UCHL5 induces apoptosis in multiple myeloma and overcomes bortezomib resistance. Blood. 2014 Jan 30;123(5):706–16.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。

MEDDEV2.7.1rev42016附中文__.71 revision 4 June 2022年Guidelines on Medical Devices Clinical Evaluation：A Guide for Manufacturers And Notified Bodies Under Directives 9342EEC and __EEC__N __IONDG Internal Market, Industry, Entrepreneurship and SMEsConsumer, Environmental and Health TechnologiesHealth technology and Cosmetics备注：中文翻译中的临床调查=临床研究，评估=评价、设备=器械、数据=资料NoteThe present Guidelines are part of a set of Guidelines relating to questions of application of EC-Directives on medical Devices. They are legally not binding. The Guidelines have been carefully drafted through a process of intensive consultation of the various interested parties (competent authorities, Commission services, industries, other interested parties) during which intermediate drafts where circulated and comments were taken up in the document. Therefore, this document reflects positions taken by representatives of interest parties in the medical devices sector.These guidelines incorporate changes introduced by Directive 2022年/47/EC amending Council Directive 90/385/EEC and Council Directive 93/42/EEC.本指南为一系列与CE―医疗器械指令应用问题相关的指南中的一部分。

Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:Senexin B is a potent, highly water–soluble and bioavailable CDK8/19 inhibitor.In Vitro: Senexin B inhibits CDK8/19 in low nanomolar range [1]. Senexin B is a newly optimized derivative of Senexin A. It has the same high selectivity for CDK8/19 and is more potent than Senexin A. Senexin B strongly reduces the emergence of estrogen independent cells. Senexin B shows synergy with fulvestrant in MCF7, T47D–ER/Luc and BT474[2].In Vivo: Pretreatment of tumor–free mice with Senexin B significantly inhibits the growth of triple–negative breast cancer (TNBC)cells inoculated into mice subsequently to Senexin B administration, indicating a general chemopreventive effect on the normal tissue “soil”. Senexin B potentiates the tumor–suppressive effect of doxorubicin on established TNBC xenografts; this effect is associated with the suppression of NFκB–mediated transcriptional induction of tumor–promoting cytokines. Senexin B inhibits invasive growth into the muscle layer in an orthotopic xenograft model of MDA–MB–468 TNBC cells. In a spleen–to–liver colon cancer metastasis model of syngeneic mouse CT26 tumors, Senexin B treatment of mice have the same effect as CDK8 knockdown in tumor cells: suppression of metastatic growth in the liver without a significant effect on primary tumor growth in the spleen [1].Senexin B suppresses tumor growth and augmentes the effects of fulvestrant in ER–positive breast cancer xenografts [2]. PROTOCOL (Extracted from published papers and Only for reference)Animal Administration: Senexin B is prepared in 6.25% 2–Hydroxypropyl–β–cyclodextrin, 1% Dextrose buffer.[2]Mouse: Once tumors reach 100–200 mm 3 volume, 4 groups of mice are treated with vehicle, Senexin B dimaleate (100 mg/kg; twice daily, oral gavage in6.25% 2–Hydroxypropyl–β–cyclodextrin, 1% Dextrose buffer) alone or in combination with fulvestrant (5 mg/mouse; s.c;once/week). Tumor volumes are measured twice weekly with calipers and volumes are calculated. After 40 days mice are euthanized, tumors are excised and weighed [2].References:[1]. Porter D, et al. Abstract PR08: Targeting tumor microenvironment with selective small–molecule inhibitors of CDK8/19. Abstracts: AACR SpecialConference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26–Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1Suppl):Abstract nr PR08. doi:10.1158/1538–7445.CHTME14–PR08[2]. McDermott MS, et al. Inhibition of CDK8 mediator kinase suppresses estrogen dependent transcription and the growth of estrogen receptor positive breast cancer. Oncotarget. 2017 Feb 21;8(8):12558–12575.Product Name:Senexin B Cat. No.:HY-101800CAS No.:1449228-40-3Molecular Formula:C 27H 26N 6O Molecular Weight:450.53Target:CDK Pathway:Cell Cycle/DNA Damage Solubility:DMSO: ≥6 mg/mLCaution: 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。

1: Identification of the substance/mixture and of the company/undertaking 1.1 Product identifier Medisanitize Universal Wipes1.2 Relevant identified uses of the substance or mixture and uses advised againstUses:Disinfection of hands and hard surfaces 1.3 Details of the supplier of the Safety Data SheetCompany name Extergeo industries ltdAddress B5 Buckshaw linkBuckshaw villageChorleyPR7 7ELUKTelephone +44(0)1772347771EmailWebsite 1.4 Emergency Telephone Number 017723477712: Hazards identification2.1 Classification of the substance or mixture2.1.1Regulation (EC) No 1272/2008(CLP)Mixture not classified as hazardous2.2 Label elements2.2.1 Label elements Contains PHMB. May produce an allergic reaction.GHS Product Identifier Medisanitize Universal WipesSignal word(s) WarningPrecautionary statement Prevention P102 - Keep out of reach of children. P103 - Read label before use.Precautionary statement: Response P101 - If medical advice is needed, have product container or label at hand.P301+P330+P331: IF SWALLOWED: Rinse mouth.P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.2.3Other hazards Not classified as PBT or vPvB.3: Composition/Information on ingredients3.1 Substances4: First-aid measures4.1Description of first aidInhalationmeasures Move affected person to fresh air at once. When breathing is difficult, properly trained personnel may assist affected person by administering oxygen. Get medical attention.Eye contact Rinse immediately with plenty of water. Remove any contact lenses and openeyelids wide apart. Continue to rinse for at least 15 minutes. Get medical attention if any discomfort continues.Skin contact Remove contaminated clothing immediately and wash skin with soap andwater. Get medical attention if any discomfort continues. Wash contaminated clothing before reuse.IngestionMove affected person to fresh air and keep warm and at rest in a position comfortable for breathing. Rinse mouth thoroughly with water. Give plenty of water to drink. Do not induce vomiting. If vomiting occurs, the head should be kept low so that vomit does not enter the lungs. Get medical attention immediately.4.2Most important symptoms and effects, both acute and delayed May cause irritation.5.1 Extinguishing media Suitable extinguishing media for the surrounding fire should be used.5.2Special hazards arising from the substance or mixtureCorrosive. In combustion emits toxic fumes.5.3 Advice for firefighters Standard protective equipment should be worn by fire fighters, inparticular eye / face protection.6: Accidental release measures6.1 Personal precautions, Large spillages are highly unlikely due to pre-saturation of liquid on protectiveequipment and fabric substrate. emergency procedures6.2 Environmental precautions Do not allow product to enter drains. Do not flush into surface water.6.3 Methods and material for Transfer to suitable, labelled containers for disposal. Clean spillagecontainment and cleaning up area thoroughly with plenty of water.6.4 Reference to other sections For recommended personal protective equipment see Section 8. For disposal see Section 13.7: Handling and storage7.1 Precautions for safe handling Avoid contact with eyes. Adopt best Manual Handling considerationswhen handling, carrying and dispensing.7.2 Conditions for safe storage,including any incompatibilities Keep out of the reach of children. Keep in a cool, dry, well ventilated area. Keep containers tightly closed.7.3 Specific end use No relevant information available.8: Exposure controls/personal protection8.1 Control parametersExposure controls No data availableExposure Limit Values No data available8.2 Engineering controlsRespiratory protection Keep in a cool, dry, well ventilated area.Individual protection measures None normally requiredEnvironmental exposure controls None normally required9: Physical and chemical properties9.1 Information on basic physical and chemical propertiesAppearance White nonwoven fabric pre-saturated with a colourlesssolutionOdour SpearmintpH No information available10: Stability and reactivity10.1 Reactivity Stable under normal conditions of storage/use.10.2 Chemical Stability Stable under recommended storage and handling conditions.10.3 Possibility of hazardousNone expectedreactions10.4 Conditions to avoid Avoid excessive heat. Do not allow to freeze.10.5 Incompatible materials Strong acids and Strong bases. Strong oxidising agents.In combustion emits toxic fumes10.6 Hazardous decompositionproducts11: Toxicological informationNo data available for this product12: Ecological informationNo data available for this product13: Disposal considerations13.1 Waste treatment Dispose of as special waste in compliance with local and national regulations.methods Empty containers can be sent to landfill after cleaning, if in compliance with local and national regulations.14: Transport informationThis preparation is not classified as “Hazardous” for transport purposes15: Regulatory information15.1 Safety, health and environmental regulations / legislation specific for the substance or mixture Notapplicable.Chemical Safety Assessment15.2 A chemical safety assessment has not been carried out for the substance or the mixture by the supplier.16: Other informationRevision information:Reviewed – no changesList of Abbreviations used in this SDS:CAS Chemical Abstracts ServiceCLP Classification, Labelling and Packaging Regulation (EC) no 1272/2008EC European Community/CommissionPBT Persistent, Bioaccumulative and ToxicREACH Registration, Evaluation, Authorisation and Restriction of Chemicals Regulation(EC) no 1907/2006vPvB very Persistent, very BioaccumulativeReferencesCLP Regulation 1272/2008ECHA Chem database of registered substancesSuppliers’ SDSR Phrases and H Statements used in Section 3Acute Tox. 4: H312 - Harmful in contact with skinAcute Tox. 4: H302 - Harmful if swallowed.Skin Corr. 1B: H314 - Causes severe skin burns and eye damage.Aquatic Acute 1: H400 - Harmful to aquatic lifeAquatic Chronic 2: H411 - Toxic to aquatic life with long lasting effects Carc.2: H351 - Suspected of causing cancer.Acute Tox. 2: H330 - Fatal if inhaled.STOT RE 1: H372 - Causes damage to organs through prolonged or repeated exposure.Eye Dam. 1: H318 - Causes serious eye damage.Skin Sens. 1B: H317 - May cause an allergic skin reaction.Aquatic Chronic 1: H410 - Very toxic to aquatic life with long lasting effectsTraining requirements for workersNo specific training required for workersThis Safety Data Sheet contains information concerning the potential risks to those involved in handling, transporting, and working with the material, as well as describing potential risks to the consumer and the environment. This information is based on our present state of knowledge and is intended to describe our products from the point of view of the safety requirements. It should not be construed as guaranteeing specific properties. This Safety Data Sheet is prepared in accordance with formatting described in the REACH Regulation (EC) No 1907/2006 and described in CLP Regulation (EC) No 1272/2008.。

Table of ContentsLB Medium (1)NZ Medium (2)SM Buffer (3)SET Buffer (4)6X Prehyb Soln (5)10 X TBE (6)10 X TAE (7)20 X SSC (8)1% SDS, 0.2 M NaOH (9)14% PEG (8000), 2M NaCl, 10 mM MgSO4 (10)20% SDS (11)1.0 M Tris, pH 8.0, 1.5 M NaCl (12)10mM Tris-HCl, pH 7.5, 10mM MgSO4 (13)10 mM Tris, 50 mM EDTA, pH 7.5 (14)10 mM Tris-HCl, 1 mM EDTA, pH 7.5 (15)3 M Sodium Acetate, pH 4.8 (16)Electrophoresis dye (17)Labelling Stop dye (18)Sequencing gel dye (19)5% Acrylamide (20)6% Acrylamide in TBE, 50% Urea (21)40% Acrylamide (22)LB Medium (1 Liter)10g Bacto-tryptone5g Bacto-yeast extract10g NaClFor forty plates add 1% agar--1g. Autoclave media. When cool, add ampicillin and pour plates. For 1L of media, add 1.8 mL amp.NZ Medium (500 mL)5 g Bacto-tryptone2.5 g Bacto-yeast extract2.5 g NaCl1.25 g MgSO4For 20 plates add 1.2% agar--6g. Autoclave and pour plates at 50o CSM Buffer (1L)5.8 g NaCl1.2 g MgSo450 mL 1M Tris-HCl, pH 7.50.1 g Gelatin (doesn't dissolve)AutoclaveUsed for phage dilution and storage.SET Buffer50 mM Tris-HCl, pH 8.0, 50 mM EDTA, 20% w/v Sucroseto make 200mL:40 g Sucrose10 mL of 1M Tris20 mL of 0.5 M EDTA, disodium saltbring to 200 mL with H206X Prehybridization Solutionto make 500 mL300 mL ddH20150 mL 20X SSC50 mL 50X Denhardt's solution1 mL 0.5 M EDTA (disodium salt)2.5 mL 20% SDS6X refers to the concentration of SSC10X TBE Buffer (for polyacrylamide gels) to make one liter:60.75 g Tris3.7 g EDTA (tetrasodium salt)30 g Boric acid10X TAE Buffer (For agarose gels)to make one liter:48.20 g Tris6.75 g NaAce3.75 g EDTA (disodium salt)Adjust pH to 7.6 with acetic acid. (Approx. 20 mL)20X SSCto make one liter:175.3 g NaCl88.2 g NaCitrateadd water to bring volume to one liter.adjust to pH 7.0 with HCl.1% SDS, 0.2 M NaOHto make 100 mL:93 mL ddH205 mL 20% SDS2 mL 10 M NaOH14% PEG (8000), 2M NaCl, 10 mM MgSO4 to make one liter:140 g PEG117 g NaCl2.46 g MgSO4For use in phage DNA preparation.20% SDSto male 250 mL:50 g of SDS in a beakerAdd stir bar and H20 last.This solution will have to be heated for the SDS to dissolve.1.0 M Tris, pH 8.0, 1.5 M NaClto make one liter:121.1 g Trizma87.6 g NaClin a volume of water less than 1L. Adjust pH with HCl, then bring to 1L with H2010 mM Tris-HCl, pH 7.5, 10 mM MgSO4to make one liter:10 mL 1 M Tris-HCl2.46 g MgSO4for use in phage DNA preparation10 mM Tris, 50 mM EDTA, pH 7.5to make 200 mL:2 mL 1 M Tris20 mL 0.5 M EDTA (tetrasodium salt)178 mL ddH20adjust pH with HCl.10 mM Tris-HCl, 1 mM EDTA, pH 7.5to make 200 mL:2.0 mL 1 M Tris-HCl, pH 7.50.4 mL 0.5 M EDTA197.6 mL ddH203 M Sodium Acetate, pH 4.8to make one liter:408.1 g NaAce (trihydrate; gets cold in soln)about 700 mL H20adjust pH with glacial acetic acid (takes a lot)Measure tru pH by dilution with water; range will be between 4.8 and 5.5.Electrophoresis Dyeto make 4 mL:3 mL 50 mM EDTA, 10 mM Tris-HCl, pH 8.01 mL glycerol20 μL BPB10 μL Xylene cyanolStop dye for labelled probe1 mL 50 mM EDTA, 10 mM Tris, pH 7.5-8.5about 200 μl glyceroladd a few grains of blue dextran (8000)Sequencing gel dyefor approx 1 mL:1 mL formamide10 μL xylene cyanol10 μl BPB3 μL 10 M NaOH5% acrylamideto make 200 mL:20 mL 10X TBE25 mL 40% acrylamide155 mL H206% Acrylamide in TBE, 50% Ureato make 500 mL:50 mL 10X TBE75 mL 40% acrylamide250 g Ureabring to 500 mL with H2O40% Acrylamide (38:2 acrylamide:bis acrylamide) to make 200 mL:76 g acrylamide4 g bis acrylamidebring to 200 mL with H2O。