Pifithrin-α-hydrobromide-Pifithrin-hydrobromide-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEPifithrin-αhydrobromideCat.No.:HY-15484CASNo.:63208-82-2Synonyms:Pifithrinhydrobromide;PFTαhydrobromide分?式:C??H??BrN?OS分?量:367.3作?靶點:MDM-2/p53;ArylHydrocarbonReceptor;Ferroptosis;Apoptosis作?通路:Apoptosis;Immunology/Inflammation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:≥50mg/mL(136.13mM)H2O:1.25mg/mL(3.40mM;Needultrasonic)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.7226mL13.6129mL27.2257mL5mM0.5445mL2.7226mL5.4451mL10mM0.2723mL1.3613mL2.7226mL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(dāng)?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(dāng)保存；體內(nèi)實驗的?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.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.81mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.81mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.81mM);ClearsolutionBIOLOGICALACTIVITY?物活性Pifithrin-αhydrobromidep53抑制劑，可阻斷其轉(zhuǎn)錄活性并阻?細(xì)胞凋亡。Pifithrin-αhydrobromide同時為arylhydrocarbonreceptor(AhR)的激動劑。IC50&Targetp53[1]AhR[2]體外研究Pifithrin-α(PFT-α)hydrobromideisawater-solublecompoundthatcouldsuppressp53proteintranscription.Pifithrin-αcansuppressglucoseoxidase(GOX)-inducedp53proteinincreaseinwholecelllysates,butcyclosporineA(CsA)failstoshowsuchaninhibitioneffect.Notably,Pifithrin-αisabletoblocktheGOX-inducedBcl-2proteinreduction.Similarly,itisPifithrin-αratherthanCsAthatabletopreventtheBaxincreasinginwholecelllysates[1].Pifithrin-αinhibitsp53-dependentapoptosisthroughanundeterminedmechanism.Pifithrin-αalsoactsasanarylhydrocarbonreceptor(AhR)agonistand.Pifithrin-αisapotentAhRagonistasdeterminedbyitsabilitytobindtheAhR,induceformationofitsDNAbindingcomplex,activatereporteractivity,andup-regulatetheclassicAhRtargetgeneCYP1A1[2].體內(nèi)研究WhentheexperimentisperformedwithPifthirin-α(PFT-α)hydrobromide,apharmacologicalp53inhibitor,thepercentageofannexinV-positiveFoxe3-/-SMCsdecreasestoWTlevels.Pifithrin-α(2.2mg/kg,i.p.)significantlyreducestheincidenceofaorticruptureandintramuralhematomasinFoxe3-/-micethatunderwenttransverseaorticconstriction(TAC)(50%to17%,PFoxe3-/-animals(P[3].PROTOCOLKinaseAssay[2]Theligandbindingcompetitionassaysareperformed.CytosoliccellextractsfromHepa-1cellsaregeneratedbytheresuspensionofthecellpelletsinHEDGbuffer[25mMHepes,1mMEDTA,1mMdithiothreitol,and10%(v/v)glycerol,pH7.5]containing0.4mMleupeptin,4mg/mLaprotinin,and0.3mMphenylmethylsulfonylfluoride,homogenization,andcentrifugationat100,000gfor45min.Aliquotsofthesupernatant(120μg)areincubatedatroomtemperaturefor2hwiththeindicatedconcentrationsofPifithrin-αinthepresenceof3nM[3H]TCDDinHEDGbuffer.Afterincubationonicewithhydroxyapatitefor30min,HEDGbufferwith0.5%Tween80isadded.Thesamplesarecentrifuged,washedtwice,resuspendedin0.2mLofscintillationfluid,andsubjectedtoscintillationcounting.Nonspecificbindingisdeterminedusinga150-foldmolarexcessofTCDFandsubtractedfromthetotalbindingtoobtainthespecificbinding.Thespecificbindingisreportedrelativeto[3H]TCDDalone[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECellAssay[1]ThehumanhepatomacelllinesHepG2(p53++)areculturedinRMPI1640mediumwith10%fetalbovineserum(FBS),and1%penicillin/streptomycinat37°Cinanatmospherecontaining5%CO2.CellsareexposedtoGOX(0-50U)for0-8hourswithorwithoutPifithrin-α(20μM/L),Pifithrin-μ(5μM/L),CsA(10μM/L),SanglifehrinA(20μM/L)andNAC(5mM/L)for1hour,respectively.Aftertreatment,cellsarecollectedandprocessedforfurtherexperiments[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]TheFoxe3-null(Foxe3-/-)miceareused.Toinvestigatetheroleofp53inFoxe3-relatedapoptosis,Pifithrin-αisadministeredbyi.p.injectionatadosageof2.2mg/kg,thendissolvedinPBS1hourbeforeTACandthenevery48hours.Animalsareeuthanized2weeksafterthesurgery,andtheascendingaortictissuesareharvestedforeitherRNA,totalprotein,histomorphometricanalysis,orTUNELassay.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JHazardMater.2021Mar15;406:124316.?EMBOJ.2022Jan5;e108946.?CellDeathDis.2022Sep6;13(9):770.?CellDeathDis.2022Apr13;13(4):343.?CellDeathDis.2020Jan22;11(1):44.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].YuW,etal.CyclosporineASuppressedGlucoseOxidaseInducedP53MitochondrialTranslocationandHepaticCellApop