TPCA-1-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETPCA-1Cat.No.:HY-10074CASNo.:507475-17-4分?式:C??H??FN?O?S分?量:279.29作?靶點(diǎn):IKK;STAT;Apoptosis作?通路:NF-κB;JAK/STATSignaling;StemCell/Wnt;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:≥100mg/mL(358.05mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.5805mL17.9025mL35.8051mL5mM0.7161mL3.5805mL7.1610mL10mM0.3581mL1.7903mL3.5805mL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(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%saline1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥7.5mg/mL(26.85mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥7.5mg/mL(26.85mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥7.5mg/mL(26.85mM);ClearsolutionBIOLOGICALACTIVITY?物活性TPCA-1?種有效，選擇性的IKK-2抑制劑，IC50值為17.9nM。TPCA-1也STAT3磷酸化、DNA結(jié)合以及反式激活的有效抑制劑。IC50&TargetIKK-2STAT317.9nM(IC50)體外研究TPCA-1inhibitslipopolysaccharide-inducedhumanmonocyteproductionofTNF-α,IL-6,andIL-8withanIC50of170to320nM[1][2].TPCA-1(0-2μM)inhibitsSTAT3phosphorylationandtransactivationinducedbycytokinesandnonreceptortyrosinekinaseindose-andtime-dependentmanner.TPCA-1completelyinhibitsSTAT3phosphorylationwithoutchangingtotalSTAT3levels[3].TPCA-1increasedsensitivitytoZD1839inbothTKIsensitivecellsandinsensitivecells[3].CellViabilityAssay[2]CellLine:humanperipheralbloodmonocytesstimulatedwithLPS.Concentration:0-10μM.IncubationTime:~24hours.Result:TPCA-1InhibitsLPS-InducedTNF-α,IL-6,andIL-8productionbyhumanmonocytes.CellViabilityAssay[3]CellLine:HCC827andH1975cells.Concentration:0-10μM.IncubationTime:0.5-2hours.Result:SuppressedproliferationofHCC827andH1975cells.LedtoaG2-Mcell-cyclearrestinHCC827butnotA549.WesternBlotAnalysis[3]CellLine:HEK-293Tcelllines.Concentration:0-2μM(beforeIL-2orIFN-αtreatment).2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:0.5-2hours.Result:InhibitedSTAT3phosphorylationandtransactivationinducedbycytokinesandnonreceptortyrosinekinaseindose-andtime-dependentmanner.體內(nèi)研究TPCA-1(3,10,or20mg/kg,i.p.)resultsinadose-dependentreductionintheseverityofmurinecollagen-inducedarthritis(CIA)[2].TPCA-1(10mg/kg,i.p.daily)inhibitsgrowthofNSCLCwithEGFRmutationandpotentiatesantitumoreffectofZD1839inxenograftmodels[3].AnimalModel:10-12weeksoldmaleDBA/1OlaHsdmice[2].Dosage:3,10,or20mg/kg.Administration:I.P.,b.i.d,fromdays1to47.Result:ReducedtheseverityanddelaystheonsetofCIA.Attenuatedexvivoantigen-inducedTcellproliferationinCIA.AnimalModel:Six-week-oldBALB/cfemalenudemiceinjectedsubcutaneouslywithHCC827cells(5×106)[3].Dosage:10mg/kg.Administration:Intraperitoneallydaily.Result:ThetumorweightinhibitionrateofTPCA-1,ZD1839,andtheircombinationare0.419(ETPCA-1),0.680(EZD1839),and0.837(Eobserved),respectively.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?SignalTransductTargetTher.2021Apr24;6(1):167.?SciTranslMed.2018Jul18;10(450).pii:eaaq1093.?ACSNano.2015Dec22;9(12):11800-11.?ProcNatlAcadSciUSA.2019Feb19;116(8):2996-3005.?PharmacolRes.2020Jul;157:104800.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].SachseF,etal.IKK-2inhibitorTPCA-1repressesnasalepithelialinflammationinvitro.Rhinology.2011Jun;49(2):168-73.[2].PodolinPL,etal.Attenuationofmurinecollagen-inducedarthritisbyanovel,potent,selectivesmallmoleculeinhibitorofIkappaB3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEKinase2,TPCA-1(2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide),occursviareductionofproinflamm[3].NanJ,etal.TPCA-1isadirectdualinhibitorofSTAT3andNF-κBandregressesmutantEGFR-associatedhumannon-smallcelllungcancers.MolCancerTher.2014Mar;13