Imatinib-STI571-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEImatinibCat.No.:HY-15463CASNo.:152459-95-5Synonyms:STI571;CGP-57148B分⼦式:C₂₉H₃₁N₇O分⼦量:493.6作⽤靶点:Bcr-Abl;PDGFR;c-Kit;SARS-CoV;Autophagy作⽤通路:ProteinTyrosineKinase/RTK;Anti-infection;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:12.5mg/mL(25.32mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0259mL10.1297mL20.2593mL5mM0.4052mL2.0259mL4.0519mL10mM0.2026mL1.0130mL2.0259mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：0.5%CMC-Na/salinewaterSolubility:11mg/mL(22.29mM);Suspendedsolution;Needultrasonic2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥1.25mg/mL(2.53mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥1.25mg/mL(2.53mM);Clearsolution4.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1.25mg/mL(2.53mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Imatinib(STI571)⼀种⼝服⽣物可⽤的酪氨酸激酶抑制剂，可选择性抑制BCR/ABL，v-Abl，PDGFR，c-kit激酶活性。Imatinib(STI571)靠近ATP结合位点结合，将其锁定在封闭或⾃我抑制的构象中，因此半竞争性抑制蛋⽩质的酶活性[1][2][3][4]。Imatinib还抑制SARS-CoV和MERS-CoV[5]。IC50&TargetBCR/ABL,v-Abl,PDGFR,c-kit[1][2][4]体外研究Imatinib(STI571)inhibitsc-Kitautophosphorylation,activationofMAPK,andactivationofAktwithoutalteringtotalproteinlevelsofc-kit,MAPK,orAkt.Theconcentrationthatproduces50%inhibitionfortheseeffectsisapproximately100nM[1].Imatinib(STI571)isveryeffective(invitroIC50of25nM)againstthechronicmyeloidleukemia-causingkinaseBcr-Abl.ImatinibalsoefficientlyinhibitsKit(invitroIC50,410nM)andPDGFR(invitroIC50,380nM)[2].Imatinib(STI571)isamulti-targetinhibitorofv-Abl,c-KitandinhibitsBcr/Abl,v-Abl,Tel/Abl,thenativePDGFβreceptor,andc-Kit,butitdoesnotinhibitSrcfamilykinases,c-Fms,Flt3,theEGFRormultipleothertyrosinekinases.ImatinibinhibitstyrosinephosphorylationandcellgrowthofBa/F3cellsexpressingBcr/Abl,Tel/Abl,Tel/PDGFβR,andTel/ArgwithanIC50ofapproximately0.5μMineachcase,butithasnoeffectonuntransformedBa/F3cellsgrowinginIL-3oronBa/F3cellstransformedbyTel/JAK2[4].TheIC50sofImatinib(STI571)isamulti-targetinhibitorofv-Abl,c-KitandonBON-1andH727cellsafterexposurefor48hare32.4and32.8μM,respectively[6].体内研究Inthephosphorothioateantisenseoligodeoxynucleotides(PS-ASODN)group,tumorgrowthisinhibitedby59.437%,whichismarkedlyhigherthanintheImatinib(STI571)isamulti-targetinhibitorofv-Abl,c-Kitandgroup(11.071%)andliposomenegativecontrolgroup(2.759%).Telomeraseactivityissignificantlylower(P[7].Imatinib(25mg/kg/day,p.o.)suppressesthegrowthofendometriotictissueandreducesthenumberofovarianfolliclesinaratmodel.Imatinibeffectivelytreatsexperimentalendometriosisbyitsinhibitoreffectsonangiogenesisandcellproliferation[8].PROTOCOLCellAssay[4]BON-1cells(7,500perwell)andNCI-H727cells(5,000perwell)areseededintoflat-bottomed96-wellplates2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEintriplicateandallowedtoadhereovernightin10%fetalbovineserum-supplementedDMEMorRPMI1640completemedium,respectively;themediumisthenexchangedforserum-freemedium(negativecontrol)orserum-freemediumcontainingserialdilutionsofImatinib.After48h(controlculturesdonotreachconfluence),thenumberofmetabolicallyactivecellsisdeterminedbythe3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromideassay,andabsorbanceismeasuredinaPackardSpectramicroplatereaderat540nm.Growthinhibitioniscalculated.Experimentsaredoneintriplicates[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[6]Administration[6][7]The40tumor-bearingSCIDmicearerandomlydividedintofourgroups(10micepergroup):thePS-ASODNgroup(5μM,eachmousereceives0.2mLbyintratumorinjectiononcedaily);Imatinibgroup(0.1mg/gbodyweight);liposomenegativecontrolgroup(0.01mL/g);andsalinegroup(0.01mL/g).Themiceineachgroupreceivetherelevanttreatmentbyintra-tumorinjectiononcedailyfromday7today28afterimplantation.After28d,themicearesacrificed,andtumorweightandlongestandshortestdiametersaremeasuredbyelectronicscaleandverniercaliper,respectively.Inhibitionoftumorgrowthiscalculated.Rats[7]AdultfemaleWistar-Albinorats(220-240g)areused.Twenty-onedaysafterthefirstsurgicalprocedure,theratsundergoasecondlaparotomytoevaluatetheoccurrenceofendometriosis.Twenty-fourratshavevisuallyconfirmedendometrioticimplantsandarerandomizedintothreegroupstoreceiveImatinib(25mg/kg/day,p.o.),Anastrozole(0.004mg/day,p.o.),ornormalsaline(0.1mL,i.p.)for14days.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•CellMetab.2022Feb7;34(3):424-440.e7.•NatBiomedEng.2018Aug;2(8):578-588.•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•NucleicAcidsRes.2021Jan8;49(D1):D1113-D1121.•EMBOMolMed.2021Mar4;e13144.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].HeinrichMC,etal.Inhibitionofc-kitreceptortyrosinekinaseactivitybySTI571,aselectivetyrosinekinaseinhibitor.Blood.2000Aug1;96(3):925-32.[2].GuidaT,etal.Sorafenibinhibitsimatinib-resistantKITandplatelet-derivedgrowthfactorreceptorbetagatekeepermutants.ClinCancerRes.2007Jun1;13(11):3363-9.[3].IqbalN,etal.Imatinib:abreakthroughoftargetedtherapyincancer.ChemotherResPract.2014;2014:357027.[4].OkudaK,etal.ARGtyrosinekinaseactivityisinhibitedbySTI571.Blood.2001Apr15;97(8):2440-8[5].YaoJC,etal.Clinicalandinvitrostudiesofimatinibinadvancedcarcinoidtumors.ClinCancerRes.2007Jan1;13(1):234-40.[6].SunXC,etal.DepletionoftelomeraseRNAinhibitsgrowthofgastrointestinaltumorstransplantedinmice.WorldJGastroenterol.2013Apr21;19(15):2340-7.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[7].YildizC,et