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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Sorafenib（同义词：Bay 43-9006）/HY-10201/500mg
商品详细Medchemexpress/Sorafenib（同义词：Bay 43-9006）/HY-10201/500mg
Medchemexpress/Sorafenib（同义词：Bay 43-9006）/HY-10201/500mg
Medchemexpress/Sorafenib（同义词：Bay 43-9006）/HY-10201/500mg
商品编号： HY-10201-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1320.00
美元价： 792.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
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商品介绍
SorafenibisapotentmultikinaseinhibitorwithIC50sof6nM,20nM,and22nMforRaf-1,B-Raf,andVEGFR-3,respectively.

CustomerValidation

  • •ACSApplMaterInterfaces.2017Apr12;9(14):12195-12202.
  • •BrJCancer.2017Sep26;117(7):974-983.
  • •Oncotarget.2017May2;8(18):29771-29784.
  • •ACSChemBiol.2017Jan20;12(1):282-290.
  • •ACSChemBiol.2016Apr15;11(4):992-1000.
  • •SciRep.2017Sep8;7(1):11006.
  • •JPharmacolExpTher.2017Aug;362(2):219-229.
  • •BiomedPharmacother.2016Dec6;86:27-31.
  • •OncolRep.2017Jan;37(1):273-280.
  • •JChromatogrBAnalytTechnolBiomedLifeSci.2017Jul17;1061-1062:220-224.
  • •ChemCentJ.2017Jan3;11:1.
  • •EndocrJ.2017Aug31.
  • •IntJClinExpPathol.2017;10(3):3033-3042.
  • •IntJClinExpPathol.2015Apr1;8(4):3871-81.
  • •ExpHematolOncol.2016Jul29;5:22.
  • •AmJDigestDis.2015;2(2):95-99.
Description

SorafenibisapotentmultikinaseinhibitorwithIC50sof6nM,20nM,and22nMforRaf-1,B-Raf,andVEGFR-3,respectively.

IC50&Target

IC50:6nM(Raf-1),20nM(VEGFR-3),22nM(BRAF),57nM(PDGFR-β),58nM(Flt3),68nM(c-KIT),90nM(VEGFR-2)[1]

InVitro

Sorafenib(BAY43-9006)alsoinhibitsBRAFwt(IC50=22nM),BRAFV599E(IC50=38nM),VEGFR-2(IC50=90nM),VEGFR-3(IC50=20nM),PDGFR-β(IC50=57nM),c-KIT(IC50=68nM),andFlt3(IC50=58nM)inbiochemicalassays.InMDA-MB-231breastcancercells,SorafenibcompletelyblocksactivationoftheMAPKpathway.CellsarepreincubatedwithSorafenib(0.01to3μM),anddose-dependentinhibitionofbasalMEK1/2andERK1/2phosphorylation(IC50,40and100nM,respectively)[1].

InVivo

Sorafenibdemonstratesbroadoralantitumorefficacyinpanelofhumantumorxenograftmodels.Sorafenibisgivenorallyat7.5to60mg/kg.Thereisnolethalityandnoincreaseinweightlossinanytreatedgrouprelativetothecorrespondingcontrolgroup.DailyoraladmiNISTrationofSorafenib(30to60mg/kg)producescompletetumorstasisduringtreatmentinfiveofthesixmodels[1].Thesurvivalrateis73.3%inDiethylnitrosamine(DENA)groupand83.3%inSorafenibgroupcomparedto100%inthenormalcontrolgroup.DENAgroupshowsasignificantincreaseinliverindex(1.51-foldincrease,p<0.05) compared="" to="" normal="" control="" group,="" while="" treatment="" with="" sorafenib="" shows="" significant="" decrease=""><0.05) in="" liver="" index="" when="" compared="" to="" dena="" group.="" the="" liver="" index="" in="" sorafenib="" group="" significantly="" decreases="" to="" lower="" than="" its="" value="" in="" the="" normal="">[2].

ClinicalTrial
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References

  • [1].WilhelmSM,etal.BAY43-9006exhibitsbroadspectrumoralantitumoractivityandtargetstheRAF/MEK/ERKpathwayandreceptortyrosinekinasesinvolvedintumorprogressionandangiogenesis.CancerRes.2004Oct1;64(19):7099-109.

    [2].El-AshmawyNE,etal.Sorafenibeffectonliverneoplasticchangesinrats:morethanakinaseinhibitor.ClinExpMed.2016Apr16.

    [3].JinW,etal.Longnon-codingRNATUC338isfunctionallyinvolvedinsorafenib-sensitizedhepatocarcinomacellsbytargetingRASAL1.OncolRep.2017Jan;37(1):273-280.

    [4].LiM,etal.ActivationofanAKT/FOXM1/STMN1pathwaydrivesresistancetotyrosinekinaseinhibitorsinlungcancer.BrJCancer.2017Aug29.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.1513mL10.7566mL21.5132mL
5mM0.4303mL2.1513mL4.3026mL
10mM0.2151mL1.0757mL2.1513mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

TotestcompoundinhibitionagainstvariousRAFkinaseisoforms,SorafenibisaddedtoamixtureofRaf-1(80ng),wtBRAF,orV599EBRAF(80ng)withMEK-1(1μg)inassaybuffer[20mMTris(pH8.2),100mMNaCl,5mMMgCl2,and0.15%β-mercaptoethanol]atafinalconcentrationof1%DMSO.TheRAFkinaseassay(finalvolumeof50μL)isinitiatedbyadding25μLof10μMγ-[33P]ATP(400Ci/mol)andincubatedat32°Cfor25minutes.PhosphorylatedMEK-1isharvestedbyfiltrationontoaphosphocellulosemat,and1%phosphoricacidisusedtowashawayunboundrADIoactivity.Afterdryingbymicrowaveheating,aβ-platecounterisusedtoquantifyfilter-boundradioactivity[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[1]

SorafenibisdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].

TheMDA-MB-231humanmammaryadenocarcinomacelllinesareplatedat2×105cellsperwellin12-welltissuecultureplatesinDMEMgrowthmedia(10%heat-inactivatedFCS)overnight.Cellsarewashedoncewithserum-freemediaandincubatedinDMEMsupplementedwith0.1%fattyacid-freeBSAcontainingvariousconcentrationsofBAY43-9006(0.01,0.03,0.1,0.3,1,3μM)in0.1%DMSOfor120minutestomeasurechangesinbasalpMEK1/2,pERK1/2,orpPKB.CellsarewashedwithcoldPBS(PBScontaining0.1mMvanadate)andlysedina1%(v/v)TritonX-100solutioncontainingproteaseinhibitors.Lysatesareclarifiedbycentrifugation,subjectedtoSDS-PAGE,transferredtonitrocellulosemembranes,blockedinTBS-BSA,andprobedwithanti-pMEK1/2(Ser217/Ser221;1:1000),anti-MEK1/2,anti-pERK1/2(Thr202/Tyr204;1:1000),anti-ERK1/2,anti-pPKB(Ser473;1:1000),oranti-PKBprimaryantibodies.Blotsaredevelopedwithhorseradishperoxidase(HRP)-conjugatedsecondaryantibodiesanddevelopedwithAmershamECLreagentonAmershamHyperfilm[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[1][2]

SorafenibisdissolvedinCremophorEL/ethanol(50:50;CremophorEL,95%ethylalcohol)at4-fold(4×)ofthehighestdose,foilwrapped,andstoredatroomtemperature(Mice)[1].

Mice[1]
FemaleNCr-nu/numiceareused.Micebearing75to150mgtumorsaretreatedorallywithSorafenib(7.5to60mg/kg),administereddailyfor9days.Ineachmodel,Sorafenibproducesdose-dependenttumorgrowthinhibitionwithnoevidenceoftoxicity,asmeasuredbyincreasedweightlossrelativetocontrolanimalsordrug-relatedlethality.Inparalleltotheantitumorefficacystudies,additionalgroupsoffourmicebearing100to200mgtumorsaretreatedorallywithvehicleorSorafenib(30to60mg/kg),administereddailyfor5days,whichistheshortesttreatmentdurationproducingcompletetumorstasisinthetreatedgroups.
Rat[2]
Inthestudy,100-to120-gmalealbinoratsareutilized.Afteracclimatizationperiod,ratsareweighedandrandomlydividedintothreegroups:Group1(normalcontrolgroup;n=10)isgiventhevehicledailyfor8weeks.Group2(DENAgroup;n=15)receivei.p.singledoseof200mg/kgDENA.Group3(Sorafenibgroup;n=12)isgivenSorafeniborallyatadoseof10mg/kgdailyfor2weeks,6weeksafterDENAi.p.injection.Attheendoftheexperiment(8weeks),ratsareweighed,anesthetizedbyether,andkilled,andtheirliversaredissected.Freshliveriswashedtwicewithice-coldsaline,driedoncleanpapertowel,andweighed.Liverindexiscalculatedasliverweight(g)/finalbodyweight(g)×100.Theliverisdividedintofiveportions:oneportionispreservedin10%formalinforhistopathologicalexaminationandtheotherportionsareimmediatelyfrozeninliquidnitrogenandstoredat−80°C.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].WilhelmSM,etal.BAY43-9006exhibitsbroadspectrumoralantitumoractivityandtargetstheRAF/MEK/ERKpathwayandreceptortyrosinekinasesinvolvedintumorprogressionandangiogenesis.CancerRes.2004Oct1;64(19):7099-109.

    [2].El-AshmawyNE,etal.Sorafenibeffectonliverneoplasticchangesinrats:morethanakinaseinhibitor.ClinExpMed.2016Apr16.

    [3].JinW,etal.Longnon-codingRNATUC338isfunctionallyinvolvedinsorafenib-sensitizedhepatocarcinomacellsbytargetingRASAL1.OncolRep.2017Jan;37(1):273-280.

    [4].LiM,etal.ActivationofanAKT/FOXM1/STMN1pathwaydrivesresistancetotyrosinekinaseinhibitorsinlungcancer.BrJCancer.2017Aug29.

MolecularWeight

464.83

Formula

C₂₁H₁₆ClF₃N₄O₃

CASNo.

284461-73-0

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥45mg/mL

SorafenibisdissolvedinDMSOandthendilutedwithsaline(thefinalDMSOconcentrationis<>[3].
Sorafenibispreparedinvehicle(saline)[4].

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

References

  • [1].WilhelmSM,etal.BAY43-9006exhibitsbroadspectrumoralantitumoractivityandtargetstheRAF/MEK/ERKpathwayandreceptortyrosinekinasesinvolvedintumorprogressionandangiogenesis.CancerRes.2004Oct1;64(19):7099-109.

    [2].El-AshmawyNE,etal.Sorafenibeffectonliverneoplasticchangesinrats:morethanakinaseinhibitor.ClinExpMed.2016Apr16.

    [3].JinW,etal.Longnon-codingRNATUC338isfunctionallyinvolvedinsorafenib-sensitizedhepatocarcinomacellsbytargetingRASAL1.OncolRep.2017Jan;37(1):273-280.

    [4].LiM,etal.ActivationofanAKT/FOXM1/STMN1pathwaydrivesresistancetotyrosinekinaseinhibitorsinlungcancer.BrJCancer.2017Aug29.

Purity:99.83%