Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVerteporfinCat.No.:HY-B0146CASNo.:129497-78-5Synonyms:CL318952分?式:C??H??N?O?分?量:718.79作?靶點(diǎn):YAP;Apoptosis;Autophagy作?通路:StemCell/Wnt;Apoptosis;Autophagy儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥200mg/mL(278.25mM)DMF:10mg/mL(13.91mM;ultrasonicandwarmingandheatto60°C)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.3912mL6.9561mL13.9123mL5mM0.2782mL1.3912mL2.7825mL10mM0.1391mL0.6956mL1.3912mL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(protectfromlight)。-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%DMF>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(3.48mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥5mg/mL(6.96mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥5mg/mL(6.96mM);ClearsolutionBIOLOGICALACTIVITY?物活性Verteporfin(CL318952)?種?于光動(dòng)?療法的光敏劑，?于消除與年齡相關(guān)的斑變性等疾病相關(guān)的眼內(nèi)異常?管。Verteporfin?種YAP抑制劑，可破壞YAP-TEAD相互作?。Verteporfin可以誘導(dǎo)細(xì)胞凋亡(apoptosis)。Verteporfin?種?噬(autophagy)抑制劑，通過抑制?噬?體形成，在早期阻斷?噬。IC50&TargetIC50:YAP-TEADinteraction體外研究VerteporfinisspecificallyselectedbyPDX-cellscreening.Theconcentrationstocause50%growthinhibition(GI50)forPhLO,PhLH,andPhLKare228nM,395nM,and538nM,respectively,whereasGI50forALL-1,TCC-Y/sr,andNPhA1are3.93μM,2.11μM,and5.61μM,respectively.GSHsignificantlyreducesthesensitivityof2outof3PDXcellstoverteporfin.VerteporfinreducesthemitochondrialmembranepotentialinPDXcells[1].VerteporfinreducesthePTX-resistanceonHCT-8/TcellsbyinhibitingYAPexpressionandcombinationtherapywithverteporfinandNSC125973showssynergismoninhibitionofYAPandcytotoxicitytoHCT-8/T[2].體內(nèi)研究Verteporfin(10mg/kg,c.s.c.)andBMS-354825significantlyreducestheleukemiacellratio,andcombinedtherapyfurtherreducedthenumberofleukemiacellsinthespleen[1].PROTOCOLCellAssay[1]PDXcellsco-culturedwithS17cellsaretreatedwith16combinationsofverteporfin(60nM,120nM,180nM,and240nM)andBMS-354825(12nM,24nM,36nM,and48nM).Theviabilitiesofcellstreatedwitheachcombinationaremeasuredafter48husingFACSAriaflowcytometer.InordertoestimatedruginteractionbetweenverteporfinandBMS-354825,anormalizedisobologramandfractionaffectedcombinationindex(CI)plotaremadeusingCompuSynsoftware.CIvaluesgreaterthan1.0indicatedantagonisticeffects,equalto1.0additiveeffects,andbelow1.0synergisticeffects.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice:PhLOcells(1.0×107/mouse)areinjectedintravenouslyinto6-week-oldmaleNOGmice,whichareAdministration[1]thentreatedwithvehicle,verteporfin(140mg/kg/day),BMS-354825(20mg/kg/day),andacombinationofthesedrugsfromdays22to28.Verteporfinisadministeredbycontinuoussubcutaneousinfusion(c.s.c.)usingAlzetosmoticpumps.Anintraperitonealinjection(i.p.)isperformedforBMS-354825.Allmicearesacrificedonday28andthechimerismofleukemiacellsisinvestigatedbyflowcytometerusingananti-humanCD19antibodyandantimouseCD45antibody.Bloodconcentrationsofverteporfinarecalculatedby2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemELCMS-2020.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CellRes.2022Jun;32(6):543-554.?CellRes.2020Mar;30(3):229-243.?CancerCell.2019Sep16;36(3):302-318.e7.?NatNeurosci.2022Jul;25(7):849-864.?SciBull.2021May15;66(9):925-936.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MorishitaT,etal.Thephotosensitizerverteporfinhaslight-independentanti-leukemicactivityforPh-positiveacutelymphoblasticleukemiaandsynergisticallyworkswithBMS-354825.Oncotarget.2016Aug2.[2].PanW,etal.VerteporfincanReversetheNSC125973ResistanceInducedbyYAPOver-ExpressioninHCT-8/TCellswithoutPhotoactivationthroughInhibitingYAPExpression.CellPhysiolBiochem.2016;39(2):481-90.[3].DonohueE,etal.Theautophagyinhibitorverteporfinmoderatelyenhancestheantitumoractivityofgemcitabineinapancreaticductaladenocarcinomamodel.J