Batoprotafib-TNO155-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBatoprotafibCat.No.:HY-136173CASNo.:1801765-04-7Synonyms:TNO155分⼦式:C₁₈H₂₄ClN₇OS分⼦量:421.95作⽤靶点:SHP2;Phosphatase作⽤通路:ProteinTyrosineKinase/RTK;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(236.99mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3699mL11.8497mL23.6995mL5mM0.4740mL2.3699mL4.7399mL10mM0.2370mL1.1850mL2.3699mL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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(5.92mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.92mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.93mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.92mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Batoprotafib(TNO155)⼀种有效的，选择性的，和具有⼝服活性野⽣型SHP2的变构抑制剂(IC50=0.011µM)。Batoprotafib有研究RTK依赖性恶性肿瘤的潜⼒，尤其晚期实体瘤。IC50&TargetIC50:0.011µM(SHP2)[1]体外研究BatoprotafibshowsanIC50of0.008µMinKYSE520pERKassayandshowsanIC50of0.100µMinKYSE5205-daycellproliferationassay.Theoff-targetIC50valuesare18µM,6.9µM,and11µMforCav1.2,VMAT,andSST3,respectively[1].Batoprotafib(0-1000nM;6days)inhibitstheviabilityofNCI-H3255,HCC827,andPC9cellswithIC50valueslowerthan1.5μM.BatoprotafibisefficaciousinEGFR-mutantNSCLCcelllines[2].BatoprotafibisefficaciousinacquiredresistancemodelsofEGFRinhibitorsanddemonstratescombinationbenefitwithEGFRinhibitors[2].BatoprotafibenhancestheefficacyofKRASG12CinhibitorsagainstKRASG12Clungandcolorectalcancers[2].Batoprotafibinhibitsimmune-suppressivemacrophagesandsynergizeswithPD1blockade[2].CellProliferationAssay[2]CellLine:PC-9,PC-9EGFRT790M/C797S,HCC827,HCC827-GR(gefinitib-resistant)Concentration:0-1000nMIncubationTime:6daysResult:InhibitedcellviabilitywithIC50sof1.56,1.38,0.77and1.38μMagainstPC-9andPC-9EGFRT790M/C797S,HCC827andHCC827-GRcells,respectively.WesternBlotAnalysis[2]CellLine:PC-14(EGFRex19del)Concentration:3μMIncubationTime:4hand24hResult:Effectivelyreducedp-ERKlevelsat4hoursbutsufferedareboundat24hours.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究Theoralbioavailabilityinmouse,ratandmoneyare78%,86%,and60%,respectively[1].Batoprotafib(20mg/kg;p.o.;twicedailyfor40days)inhibitstumorgrowthandismoreeffectivewhencombinedwithDabrafenib(HY-14660)plusTrametinib(HY-10999)innudemicebearingHT-29xenografts[2].Batoprotafib(7.5mg/kg;p.o.;b.i.d.orq.d.for36days)plusJDQ-443(HY-139612)(100mg/kg;p.o.;q.d.)improvesthesingle-agentactivityofJDQ443inKRASG12C-mutatedcell-derived(CDX)modelsinnudemice[3].AnimalModel:FemaleathymicnudemicebearingHT-29xenografts[2]Dosage:20mg/kgaloneor10mg/kgincombinationwithDabrafenibandTrametinibAdministration:PO,twicedailyfor40daysResult:Resultedinmoderatetumorgrowthinhibition.Maintainedtumorstasisformorethan40dayswhencombinedwithDabrafenibplusTrametinib.户使⽤本产品发表的科研⽂献•EurJCancer.2021Oct26;159:16-23.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LiuC,etal.CombinationswithAllostericSHP2InhibitorTNO155toBlockReceptorTyrosineKinaseSignaling.ClinCancerRes.2021Jan1;27(1):342-354.[2].WeissA,etal.Discovery,PreclinicalCharacterization,andEarlyClinicalActivityofJDQ443,aStructurallyNovel,Potent,andSelectiveCovalentOralInhibitorofKRASG12C.CancerDiscov.2022Jun2;12(6):1500-1517.[3].TNO155:SHP2inhibitor