N-Desethyl-Sunitinib-hydrochloride-SU-12662-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEN-DesethylSunitinibhydrochlorideCat.No.:HY-138813Synonyms:SU-12662hydrochloride分⼦式:C₂₀H₂₄ClFN₄O₂分⼦量:406.88作⽤靶点:Others作⽤通路:Others储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:50mg/mL(122.89mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4577mL12.2886mL24.5773mL5mM0.4915mL2.4577mL4.9155mL10mM0.2458mL1.2289mL2.4577mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(6.14mM);Clearsolution;Needultrasonic1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(6.14mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性N-DesethylSunitinib(SU-12662)(hydrochloride)Sunitinib的代谢物。Sunitinib有效的，ATP竞争的VEGFR，PDGFRβ和KIT抑制剂，能够抑制VEGFR-1，VEGFR-2，VEGFR-3，PDGFRβ和KIT的活性，Ki值分别为2，9，17，8和4nM[1]。体外研究SunitinibalsopotentlyinhibitsKitandFLT-3[1].SunitinibisapotentATP-competitiveinhibitorofVEGFR2(Flk1)andPDGFRβwithKiof9nMand8nM,respectively,displaying>10-foldhigherselectivityforVEGFR2andPDGFRthanFGFR-1,EGFR,Cdk2,Met,IGFR-1,Abl,andsrc.Inserum-starvedNIH-3T3cellsexpressingVEGFR2orPDGFRβ,SunitinibinhibitsVEGF-dependentVEGFR2phosphorylationandPDGF-dependentPDGFRβphosphorylationwithIC50of10nMand10nM,respectively.SunitinibinhibitsVEGF-inducedproliferationofserum-starvedHUVECswithIC50of40nM,andinhibitsPDGF-inducedproliferationofNIH-3T3cellsoverexpressingPDGFRβorPDGFRαwithIC50of39nMand69nM,respectively[2].Sunitinibinhibitsphosphorylationofwild-typeFLT3,FLT3-ITD,andFLT3-Asp835withIC50of250nM,50nM,and30nM,respectively.SunitinibinhibitstheproliferationofMV4;11andOC1-AML5cellswithIC50of8nMand14nM,respectively,andinducesapoptosisinadose-dependentmanner[3].体内研究Sunitinib(20-80mg/kg/day)exhibitsbroadandpotentdose-dependentanti-tumoractivityagainstavarietyoftumorxenograftmodelsincludingHT-29,A431,Colo205,H-460,SF763T,C6,A375,orMDA-MB-435,consistentwiththesubstantialandselectiveinhibitionofVEGFR2orPDGFRphosphorylationandsignalinginvivo.Sunitinib(80mg/kg/day)for21daysleadstocompletetumorregressioninsixofeightmice,withouttumorre-growingduringa110-dayobservationperiodaftertheendoftreatment.SecondroundoftreatmentwithSunitinibremainsefficaciousagainsttumorsthatarenotfullyregressedduringthefirstroundoftreatment.SunitinibtreatmentresultsinsignificantdecreaseintumorMVD,withappr40%reductioninSF763Tgliomatumors.SU11248treatmentresultsinacompleteinhibitionofadditionaltumorgrowthofluciferase-expressingPC-3Mxenografts,despitenoreductionintumorsize[2].Sunitinibtreatment(20mg/kg/day)dramaticallysuppressesthegrowthsubcutaneousMV4;11(FLT3-ITD)xenograftsandprolongssurvivalintheFLT3-ITDbonemarrowengraftmentmodel[3].户使⽤本产品发表的科研⽂献•ActaPharmacolSin.2016Jul;37(7):930-40.•BiolPharmBull.2021;44(10):1565-1570.•BiomedChromatogr.2015May;29(5):679-88.•SSRN.23Sep2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE[1].SunL,etal.Discoveryof5-[5-fluoro-2-oxo-1,2-dihydroindol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylicacid(2-diethylaminoethyl)amide,anoveltyrosinekinaseinhibitortargetingvascularendothelialandplatelet-derivedgrowthfactorreceptortyrosinekinase.JMedChem.2003;46(7):1116-1119.[2].MendelDB,etal.InvivoantitumoractivityofSU11248,anoveltyrosinekinaseinhibitortargetingvascularendothelialgrowthfactorandplatelet-derivedgrowthfactorreceptors:determinationofapharmacokinetic/pharmacodynamicrelationship.ClinCancerRes.2003;9(1):327-337.[3].O'FarrellAM,etal.SU11248isanovelFLT3tyrosinekinaseinhibitorwithpotentactivityinvitroandinvivo.Blood.2003;101(