Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEImatinibMesylateCat.No.:HY-50946CASNo.:220127-57-1Synonyms:STI571Mesylate;CGP-57148BMesylate分?式:C??H??N?O?S分?量:589.71作?靶點:c-Kit;Bcr-Abl;PDGFR;Autophagy作?通路:ProteinTyrosineKinase/RTK;Autophagy儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(211.97mM;Needultrasonic)H2O:≥50mg/mL(84.79mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6957mL8.4787mL16.9575mL5mM0.3391mL1.6957mL3.3915mL10mM0.1696mL0.8479mL1.6957mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(3.53mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.53mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.53mM);Clearsolution4.請依序添加每種溶劑：PBSSolubility:100mg/mL(169.57mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性ImatinibMesylate(STI571Mesylate)?種酪氨酸激酶抑制劑，可抑制c-Kit，Bcr-Abl和PDGFR(IC50=100nM)。IC50&TargetIC50:~100nM(c-Kit,Bcr-Abl,andPDGFR)[1]體外研究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].體內(nèi)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?邊的抑制劑?師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.戶使?本產(chǎn)品發(fā)表的科研?獻?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?邊的抑制劑?師www.MedChemE[1].HeinrichMC,etal.Inhibitionofc-kitreceptortyrosinekinaseactivitybySTI571,aselectivetyrosinekinaseinhibitor.Blood.2000Aug1;96(3):925-32.[2].GuidaT,etal.Sorafenibinhibitsimatinib-resistantKITandplatelet-derivedgrowthfactorreceptorbetagatekeepermutants.