HPK1-IN-55-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEHPK1-IN-55Cat.No.:HY-170365CASNo.:3048537-58-9分⼦式:C₃₀H₃₄N₈O₃分⼦量:554.64作⽤靶点:MAP4K作⽤通路:MAPK/ERKPathway储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY⽣物活性HPK1-IN-55(compound19)⼀种选择性且具有⼝服活性的造⾎祖细胞激酶1(HPK1)抑制剂，其IC50为[1]。IC50&TargetHPK150)体外研究HPK1-IN-55(0.5-10000nM,5h)demonstratesenzymaticinhibition(IC5050=43.3nM)inhumanPBMCs[1].HPK1-IN-55(0.001-100nM)stimulatesIL-2andIFN-γreleasewithEC50valuesof38.8and49.2nM,respectivelyinpurifiedhumanpanTcells[1].HPK1-IN-55(0.00457-10μM,72h)increasesTcellproliferationatlow,intermediateandhighconcentrationsinhumanpanTcells[1].CellProliferationAssay[1]CellLine:humanpanTcellsConcentration:0.00457,0.01372,0.04115,0.12346,0.37037,1.11111,3.33333,10μMIncubationTime:72hResult:IncreasedTcellproliferationatlow,intermediateandhighconcentrationsinhumanpanTcells.1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE体内研究HPK1-IN-55(1.5-12mg/kg,p.o.,b.i.d,5weeks)exertsgoodantitumoreffectsasamonotherapy,whichshowsanadditiveeffectintheCT26modelandasynergisticeffectintheMC38modelwhencombinedwithanti-PD-1[1].HPK1-IN-55(1mg/kg,i.v.,2mg/kg,p.o.)exhibitsmoderateclearance(Clp=11.41mL/min/kg)aswellasgoodoralexposure(DNAUC(0−24h)=560.5h•ng/mL)andbioavailability(F%=42.0)inmonkeys[1].HPK1-IN-55(1.5-12mg/kg,p.o.,b.i.d,5weeks)exhibitsgoodtargetengagementintheCT26model[1].InVivoPharmacokineticsofHPK1-IN-55.HPK1-IN-55beagledogsIVClp(mL/min/kg)Vd(L/kg)11.445.58beagledogsPODNAUC(0-24h)(h·ng/ml)t1/2(h)F(%)5637.6541.5cynomonkeysIVClp(mL/min/kg)Vd(L/kg)11.415.07cynomonkeysPODNAUC(0-24h)(h·ng/ml)t1/2(h)F(%)560.58.7342AnimalModel:Balb/cmicebearingtheCT26murinecolorectalcancertumor[1].Dosage:3,10,or30mg/kgAdministration:p.o.,b.i.d,24hResult:Animalsreceivinga10and30mg/kgdoseexhibitedafreeplasmaconcentrationthatinhibitedpSLP76>50%inthespleenformorethan6h,whereasanimalsreceivingthe3mg/kgdosedidnotexhibitthissustainedreduction.AnimalModel:Balb/cmiceinjectedwithCT26cells[1].Dosage:1.5,12mg/kgAdministration:p.o.,b.i.d,5weeksResult:Exhibitedagoodantitumorresponsewithatumorgrowthinhibition(TGI)valueof64.3%.AnimalModel:Balb/cmiceinjectedwithMC38cells[1].Dosage:3,12mg/kgAdministration:p.o.,b.i.d,5weeks2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:DemonstratedsimilarantitumorefficacyintheMC38modelwithaTGIvalueof34.9%forthe3mg/kggroupand59.4%forthe12mg/kggroup.REFERENCES[1].PengJ,et.al.DiscoveryofPyridine-2-CarboxamidesDerivativesasPotentandSelectiveHPK1InhibitorsfortheTreatmentofCancer.JMedChem.2024Dec12;67(23):21520-21544.McePdfHeightCaution:Producthasnotbeenfullyvalidatedfor