Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETirbanibulinMesylateCat.No.:HY-10340BCASNo.:1080645-95-9Synonyms:KX2-391Mesylate;KX01Mesylate分?式:C??H??N?O?S分?量:527.63作?靶點(diǎn):Src;Microtubule/Tubulin作?通路:ProteinTyrosineKinase/RTK;CellCycle/DNADamage;Cytoskeleton儲(chǔ)存?式:-20°C,protectfromlight,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light,storedundernitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(189.53mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.8953mL9.4763mL18.9527mL5mM0.3791mL1.8953mL3.7905mL10mM0.1895mL0.9476mL1.8953mL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,storedundernitrogen)。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(4.74mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(4.74mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.74mM);ClearsolutionBIOLOGICALACTIVITY?物活性TirbanibulinMesylate(KX2-391Mesylate)?種有效的Src抑制劑，在腫瘤細(xì)胞中，GI50值為9-60nM。IC50&TargetGI50:9nM(Src,inHuH7cells),13nM(Src,inPLC/PRF/5cells),26nM(Src,inHep3Bcells),60nM(Src,inHepG2cells)[1]體外研究TirbanibulinMesylate(KX2-391Mesylate)isaSrcinhibitorthatisdirectedtotheSrcsubstratepocket.Tirbanibulin(KX2-391)showssteepdose-responsecurvesagainstHuh7(GI50=9nM),PLC/PRF/5(GI50=13nM),Hep3B(GI50=26nM),andHepG2(GI50=60nM),fourhepaticcellcancer(HCC)celllines[1].TirbanibulinMesylate(KX2-391Mesylate)isfoundtoinhibitcertainleukemiacellsthatareresistanttocurrentcommerciallyavailabledrugs,suchasthosederivedfromchronicleukemiacellswiththeT3151mutation.TirbanibulinMesylate(KX2-391Mesylate)isevaluatedinengineeredSrcdrivencellgrowthassaysinNIH3T3/c-Src527FandSYF/c-Src527FcellsandexhibitsGI50with23nMand39nM,respectively[2].體內(nèi)研究OrallyadministeredTirbanibulinMesylate(KX2-391Mesylate)isshowntoinhibitprimarytumorgrowthandtosuppressmetastasis,inpre-clinicalanimalmodelsofcancer[2].PROTOCOLCellAssay[1]LivercelllinesincludingHuh7,PLC/PRF/5,Hep3B,andHepG2areroutinelyculturedandmaintainedinbasalmediumcontaining2%fetalbovineserum(FBS)at37°Cand5%CO2.Cellsareseededat4.0×103/190μLand8.0×103/190μLperwellof96-wellplateinbasalmediumcontaining1.5%FBS.Theseareculturedovernightat37°Cand5%CO2priortotheadditionofTirbanibulin(KX2-391),atconcentrationsrangingfrom6,564to0.012nMintriplicates.Treatedcellsareincubatedfor3days.TenμLsof3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)solution(5mg/mL)isthenaddedtoeachwellonday3andcellsincubatedfor4hours.Theformazanproductisdissolvedwith10%SDSindiluteHCl.Opticaldensityat570nmismeasured.Forcomparisonofactivityandpotency,parallelexperimentsareperformedusingTirbanibulin(KX2-391).Growthinhibitioncurves,50%inhibitionconcentration(GI50),and80%inhibitionconcentration(GI80)aredeterminedusingGraphPadPrism5statisticalsoftware.Dataarenormalizedtorepresentpercentageofmaximumresponseaswellasreportedinopticaldensityatwavelengthof570nm(OD570)signalformat.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?JBiolChem.2019Nov29;294(48):18099-18108.?BrainRes.2020Jun1;1736:146782.?HarvardMedicalSchoolLINCSLIBRARYSeemorecustomervalidationsonwww.MedChemEREFERENCES[1].LauGM,etal.ExpressionofSrcandFAKinhepatocellularcarcinomaandtheeffectofSrcinhibitorsonhepatocellularcarcinomainvitro.DigDisSci,2009,54(7),1465-1474.[2].Fallah-TaftiA,etal.ThiazolylN-benzyl-substitutedacetamidederivatives:synthesis,Srckinaseinhibitoryandanticanceractivities.EurJMedChem,2011,46(1