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

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEImatinibMesylateCat.No.:HY-50946CASNo.:220127-57-1Synonyms:STI571Mesylate;CGP-57148BMesylate分⼦式:C₃₀H₃₅N₇O₄S分⼦量:589.71作⽤靶点:c-Kit;Bcr-Abl;PDGFR;Autophagy作⽤通路:ProteinTyrosineKinase/RTK;Autophagy储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:125mg/mL(211.97mM;Needultrasonic)H2O:≥50mg/mL(84.79mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6957mL8.4787mL16.9575mL5mM0.3391mL1.6957mL3.3915mL10mM0.1696mL0.8479mL1.6957mL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(sealedstorage,awayfrommoisture)。-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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.53mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.53mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.53mM);Clearsolution4.请依序添加每种溶剂：PBSSolubility:100mg/mL(169.57mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性ImatinibMesylate(STI571Mesylate)⼀种酪氨酸激酶抑制剂，可抑制c-Kit，Bcr-Abl和PDGFR(IC50=100nM)。IC50&TargetIC50:~100nM(c-Kit,Bcr-Abl,andPDGFR)[1]体外研究Imatinib(STI571)Mesylateinhibitsc-Kitautophosphorylation,activationofMAPK,andactivationofAktwithoutalteringtotalproteinlevelsofc-kit,MAPK,orAkt.Theconcentrationthatproduces50%inhibitionfortheseeffectsisapproximately100nM[1].Imatinib(STI571)mesylateisveryeffective(invitroIC50of25nM)againstthechronicmyeloidleukemia-causingkinaseBcr-Abl.ImatinibalsoefficientlyinhibitsKit(invitroIC50,410nM)andPDGFR(invitroIC50,380nM)[2].Imatinib(STI571)mesylateisamulti-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[3].ImatinibmesylateselectivelyinhibitstheactivityofBcr/Abl,c-KitandPDGFRkinases.Imatinibmesylaterevealsdistinctandrapidantileukemicactivityinchronicmyelogenousleukemia(CML)andPhiladelphia-positive(Ph+)acutelymphoblasticleukemia(ALL)[4].体内研究AnimalstreatedwithImatinibMesylateshowadecreaseofmeanbodyweightthroughoutthewholestudy.BodyweightlossisnoticeableinmicefromgroupsthatreceivechemotherapyandthevitaminDanalogcombinedtreatment.ThebodyweightdecreaseofmicetreatwithbothcombinedImatinibmesylateandPRI-2191isthehighest(15%)onDay22oftheexperiment,butafterthatday,micestarttorecover[4].InaratIschemia/reperfusioninjury(IRI)model,Imatinibmesylateattenuateslunginjurybyanantipermeabilityandantiinflammatoryeffect.ThedeliveryandfunctionofImatinibmesylateinthelungisalsoconfirmedinthismodel[5].PROTOCOLCellAssay[4]TestedA549cellsareplacedin96-wellflat-bottomplatesatadensityof5×103cellsperwell24hbeforetheadditionofthetestcompounds.Thecellsareincubatedfor96hwithtwodifferentconcentrations(10and100nM)ofPRI-2191andconcurrentlywithvariousconcentrationsofImatinibmesylate(10,100,1000and2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE10,000ng/mL)andothercytostaticdrugs(Docetaxel(DTX)orIdarubicin(ID):0.1,1,10,100ng/mL;Cisplatin(CIS):1,10,100,1000ng/mL).ThesulforhodamineB(SRB)assayisperformedtoevaluatethecytotoxiceffect.Asaresult,IC50iscalculatedforeachseparateexperimentinCheburator0.4,DmitryNevozhaysoftware[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[4]Administration[4][5]NOD/SCIDfemalemice,12-16weeksold,bodyweightof20-25g,areused.Micearesubcutaneously(s.c.)inoculatedintherightflankoftheabdomenwithA549tumorcellssuspension(5×106cellsin0.2mLofHank’smediumpermouse,Day0)andthenarerandomizedintogroupsreceivingvariedcombinationsofvitaminDanalogsandchemotherapeutics.Oneoutoftwoexperimentalprotocolsisappliedintherespectiveexperiments:1.ThetreatmentisstartedfromDay7afterinoculationoftumorcells(whentumorsbecomepalpable).Imatinibmesylateisadministeredintraperitoneally(i.p.)atadoseof75mg/kg/day,dailyfor19days(fromDays7-25).PRI-2191isadministereds.c.orbyoralgavageatadoseof2μg/kg/day,3timesaweek(onDays7,12,14,16,19,21and23).2.ThetreatmentisstartedfromDay7afterinoculationoftumorcells(whentumorsbecomepalpable).Imatinibmesylateisadministeredintraperitoneally(i.p.)atadoseof50mg/kg/day,dailyfor13days(fromDays7-19).PRI-2191andPRI-2205areadministereds.c.atdosesof1or10μg/kg/day,respectively,3timesaweek(onDays7,10,12,14,17,19,21,24and26).Attheendoftheexperiments,bloodiscollectedunderanesthesia;then,themicearesacrificed.Rats[5]MaleLewisratsweighing270to320gareusedintheexperiments.Imatinibmesylate(50mg/kg)isinjected

intraperitoneallyintheImatinibgroup(n=7),and0.5mLof20%DMSOwithoutImatinibisadministeredinthe

vehiclegroup(n=7).Thedoseof25mg/kgispreliminarilytested,anditproducesalittleimprovementinlung

functionwithoutstatisticalsignificance.Thedoseof50mg/kgandintraperitonealadministrationareadopted

basedonthisresultandpastreports.Theanimalsundergoleftthoracotomy,andthelefthilumisoccluded

withasmallmetallicclamp.Theocclusionisperformed20minutesafterImatiniborvehicleadministration.

Duringclamping,thetidalvolume(TV)andrespiratoryrate(RR)areadjustedto8mL/kgand80breaths/min,

respectively.After90minutesofischemia,theclampisremovedandreperfusionismaintainedfor120

minutes.Duringreperfusion,bloodflowandventilationarerestoredinthebilaterallung.Intheshamgroup

(n=6),theanimalsareheparinized,thoracotomized,andventilatedfor210minutes.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.MedChemEREFERENCES3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].HeinrichMC,etal.Inhibitionofc-kitreceptortyrosinekinaseactivitybySTI571,aselectivetyrosinekinaseinhibitor.Blood.2000Aug1;96(3):925-32.[2].GuidaT,etal.Sorafenibinhibitsimatinib-resistantKITandplatelet-derivedgrowthfactorreceptorbetagatekeepermutants.