Trk-IN-20-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETrk-IN-20Cat.No.:HY-150561CASNo.:2460924-63-2分?式:C??H??F?N?分?量:376.4作?靶點(diǎn):TrkReceptor作?通路:NeuronalSignaling;ProteinTyrosineKinase/RTK儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Trk-IN-20?種3-?烯咪唑衍?物，Trk抑制劑。Trk-IN-20通過抑制磷酸化來(lái)抑制Trk激酶功能，抑制TrkA/B/C的IC50s分別為1.6nM、2.9nM和2.0nM。IC50&TargetTrkATrkBTrkC1.6nM(IC50)2.9nM(IC50)2.0nM(IC50)體外研究NTRK1isaproto-oncogeneincoloncancer,Trkinhibitorshavebeendetectedtoagainstavarietyofhumancancers[1].Trk-IN-20(compound7mb)(0.031,or0.018μM,respectively;72h)exhibitsstronginhibitionagainsttheLarotrectinib-resistantcellswithNTRK1-G667CorNTRK3-G696AmutationswithIC50sof0.031and0.018μM,respectively[1].Trk-IN-20(compound7mb)(9-22nM;72h)inhibitsBaF3murinecellsstablytransformedwithNTRKoncogenicfusionsincludingCD74-NTRK1,ETV6-NTRK2andETV6-NTRK3withIC50sof15,22,and9nM,respectively[1].Trk-IN-20(compound7mb)(0.32,1.6,8,40,200;6h)inhibitsactivationofTrkanditsdownstreamproteinsinBaF3-CD74-NTRK1,BaF3-ETV6-NTRK2,BaF3-ETV6-NTRK3cells[1].Trk-IN-20(compound7mb)tightlyboundtoATP-bindingsiteofTrkA,TrkB,andTrkCwithbindingconstant(Kd)valuesof1.6,3.1and4.9nM,respectively[1].WesternBlotAnalysis[1]CellLine:BaF3-CD74-NTRK1,BaF3-ETV6-NTRK2,BaF3-ETV6-NTRK3cells1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEConcentration:0,0.32,1.6,8,40,200nMIncubationTime:6hoursResult:InhibitedthephosphorylationofTrkA/B/CandtheirdownstreamsignalingmoleculesERK,AKT,andPLC-γ1.AndalsoinducedpartialdegradationofTrkproteininBaF3-ETV6-NTRK2,BaF3-ETV6-NTRK3cells.體內(nèi)研究Trk-IN-20(compound7mb)(p.o.;10mg/kg)showsshorthalf-lifeof1.39hoursandaloworalbioavailabilityof8.79%inrats[1].AnimalModel:PharmacokineticProfileofTrk-IN-20(Compound7mb)inRats[1]Dosage:Administration:Result:RouteDose(mg/kg)AUC0-∞(μM.h)Cmax(μM)T1/2(h)CL(L/h/kg)BA(%)i.v.23.696.771.391.44/p.o.101.620.361.13-8.79REFERENCES[1].DuanY,etal.Design,synthesis,andStructure-ActivityRelationships(SAR)of3-vinylindazolederivativesasnewselectivetropomyosinreceptorkinases(Trk)inhibitors.EurJMedChem.2020Oct1.203:112552.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forrese