Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERho-Kinase-IN-2Cat.No.:HY-150640CASNo.:2573071-18-6分?式:C??H??FN?O?分?量:372.44作?靶點(diǎn):ROCK作?通路:CellCycle/DNADamage;Cytoskeleton;StemCell/Wnt;TGF-beta/Smad儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Rho-Kinase-IN-2(Compound23)?種具有?服活性的、選擇性的和中樞神經(jīng)系統(tǒng)(CNS)滲透性的Rho激酶(ROCK)抑制劑(ROCK2IC50=3nM)。Rho-Kinase-IN-2可?于亨廷頓病的研究。IC50&TargetROCK23nM(IC50)體外研究Rho-Kinase-IN-2(0-10mM,1hour)treatmentshowsanincreaseinAKTphosphorylationandadecreaseinMYPT1phosphorylation[1].WesternBlotAnalysis[1]CellLine:A7r5andPANC1cellsConcentration:0-10mMIncubationTime:1hourResult:Showedconcentration-dependenteffects,leadingtoanincreaseinAKTphosphorylation(EC50=28nM)andadecreaseinMYPT1phosphorylation(IC50=14nM).體內(nèi)研究Rho-Kinase-IN-2(oraladiministration;10mg/kg;6times;0.5,1,2,4,8,and12h)treatmentshowsdose-andtime-dependentROCK1andROCK2targetengagement[1].Rho-Kinase-IN-2(oraladiministration;10or20mg/kg;QDorBID;2weeks)treatmentshowsexcellenttolerabilityassessment[1].1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemERho-Kinase-IN-2(oraladiministration;1-20mg/kg;once)treatmentshowsadirectdose-andtime-dependentrelationshipbetweenbrainexposureandMYPT1phosphorylationstatus[1].Rho-Kinase-IN-2(oraladiministration;10or20mg/kg;once)treatmentdecreasesinthemeanarterial,systolic,diastolicbloodpressure,andheartrate[1].Rho-Kinase-IN-2(oraladiministration;10mg/kg;twiceaday;90days)treatmentleadstolower-than-expectedbrainconcentrations[1].AnimalModel:MaleC57BL/6mice[1]Dosage:10mg/kgAdministration:Oraladiministration;10mg/kg;6times;0.5,1,2,4,8,and12hResult:Observeddose-andtime-dependentROCK1andROCK2TE,withafreebrainKiNativROCK1andROCK2IC50=-6nM.AnimalModel:3?4monthsoldheterozygoteQ175DNKIandwild-typelittermatemice[1]Dosage:10or20mg/kgAdministration:Oraladiministration;10or20mg/kg;onceadayortwiceaday;2weeksResult:Scoredneurologicalindexnormallyatalldosesalthoughaslightlossinbodyweight(-2%)inthe20mg/kgtreatmentgroup.AnimalModel:HeterozygoteHTTzQ175DNknock-inmice[1]Dosage:1-20mg/kgAdministration:Oraladiministration;1-20mg/kg;onceResult:RemainedoverMYPT1IC50forover2hofthefreebrainat10mg/kg,andobservedthedose-andtime-dependentinhibitionofMYPT1phosphorylationinthestriatumfollowingacuteinvivodosing.AnimalModel:CD1mice[1]Dosage:10and20mg/kgAdministration:Oraladiministration;10or20mg/kg;onceResult:Observedthedecreasesinthemeanarterial(maximumchangeof61.0±8.5mmHgfrombaseline),systolic(maximumchangeof59.5±8.4mmHgfrombaseline),diastolicbloodpressure(maximumchangeof56.4±9.0mmHgfrombaseline),andheartrate(maximumchangefrompredoseof107bpm)whencomparedtothecontrolgroupfrom-0.5to2hpostdose.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAnimalModel:HeterozygoteQ175DNKImousemodelofHD[1]Dosage:10mg/kgAdministration:Oraladiministration;10mg/kg;twiceaday;90daysResult:Ledtolower-than-expectedbrainconcentrationscomparedtosingledosing.REFERENCES[1].TammyLadduwahetty,etal.IdentificationofaPotent,Selective,andBrain-PenetrantRhoKinaseInhibitoranditsActivityinaMouseModelofHuntington'sDisease.JMedChem.2022Jul11.McePdfHeightCaution:Producthas