Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEOrantinibCat.No.:HY-10517CASNo.:252916-29-3Synonyms:SU6668;TSU-68分?式:C??H??N?O?分?量:310.35作?靶點(diǎn):PDGFR;FGFR;VEGFR;Apoptosis作?通路:ProteinTyrosineKinase/RTK;Apoptosis儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥28mg/mL(90.22mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2222mL16.1108mL32.2217mL5mM0.6444mL3.2222mL6.4443mL10mM0.3222mL1.6111mL3.2222mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥10mg/mL(32.22mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)rantinib(SU6668;TSU-68)多靶點(diǎn)的受體酪氨酸激酶抑制劑，對(duì)Flt-1，PDGFRβ和FGFR1的Ki值分別為2.1μM，8nM和1.2μM。IC50&TargetPDGFRβFGFR1Flt-18nM(Ki)1.2μM(Ki)2.1μM(Ki)體外研究Orantinib(SU6668;0.03-10μM)showsinhibitoryactivityagainsttyrosinephosphorylationofKDRinVEGFstimulatedHUVECs,andalsoblocksPDGF-stimulatedPDGFRβtyrosinephosphorylationinNIH-3T3cellsoverexpressingPDGFRβ.Orantinib(≥10μM)inhibitsacidicFGF-inducedphosphorylationoftheFGFR1substrate2.However,Orantinib(upto100μM)hasnoeffectonEGF-stimulatedEGFRtyrosinephosphorylationinNIH-3T3cellsoverexpressingEGFR.Furthermore,OrantinibinhibitsVEGF-drivenandFGF-drivenmitogenesisofHUVECswithmeanIC50of0.34μMand9.6μM,respectively[1].InhumanmyeloidleukemiaMO7Ecells,Orantinib(SU6668)inhibitsthetyrosineautophosphorylationofstemcellfactor(SCF)receptor,c-kit,withIC50of0.1-1μM,aswellasERK1/2phosphorylation.Inaddition,OrantinibsuppressesSCF-inducedproliferationofMO7EcellswithanIC50of0.29μM,andinducesapoptosis[2].體內(nèi)研究Orantinib(SU6668;75-200mg/kg)causestumorgrowthinhibitiononseveraltumortypesinxenograftmodelsinathymicmice,suchasA375,Colo205,H460,Calu-6,C6,SF763T,andSKOV3TP5cells.Orantinib(75mg/kg)alsoinhibitstumorangiogenesisofC6gliomaxenografts[1].InatumormodelofHT29humancoloncarcinoma,Orantinib(200mg/kg)decreasestheaveragevesselpermeabilityandaveragefractionalplasmavolumeinthetumorrimandcore.Orantinibenhancesabnormalstromaldevelopmentattheperipheryofcarcinomas[3].Moreover,Orantinib(TSU-68;200mg/kg)augmentstheeffectofchemotherapeuticinfusioninarabbitVX2livertumormodel[4].戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?PLoSGenet.2022Jun27;18(6):e1010292.?Patent.US20180263995A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LairdAD,etal.SU6668isapotentantiangiogenicandantitumoragentthatinducesregressionofestablishedtumors.CancerRes,2000,60(15),4152-4160.[2].SmolichBD,etal.TheantiangiogenicproteinkinaseinhibitorsSU5416andSU6668inhibittheSCFreceptor(c-kit)inahumanmyeloid2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEleukemiacelllineandinacutemyeloidleukemiablasts.Blood,2001,97(5),1413-1421.[3].MarzolaP,etal.InvivoassessmentofantiangiogenicactivityofSU6668inanexperimentalcoloncarcinomamodel.ClinCancerRes,2004,10(2),739-750.[4].KimHC,etal.AugmentationofchemotherapeuticinfusioneffectbyTSU-68,anoraltargetedantiangiogenicagent,inarabbitVX2livertumormodel.CardiovascInterventRadiol.2012Feb;35(1):168-75McePdfHeightCaution: