Larotrectinib-LOXO-101-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemELarotrectinibCat.No.:HY-12866CASNo.:1223403-58-4Synonyms:LOXO-101;ARRY-470分?式:C??H??F?N?O?分?量:428.44作?靶點:TrkReceptor;Apoptosis作?通路:NeuronalSignaling;ProteinTyrosineKinase/RTK;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數據體外實驗DMSO:≥4.6mg/mL(10.74mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.3340mL11.6702mL23.3405mL5mM0.4668mL2.3340mL4.6681mL10mM0.2334mL1.1670mL2.3340mL請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據您的實驗動物和給藥?式選擇適當的溶解?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結果的可靠性，澄的儲備液可以根據儲存條件，適當保存；體內實驗的?作液，建議您現?現配，當天使?；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?；如在配制過程中出現沉淀、析出現象，可以通過加熱和/或超聲的?式助溶)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(5.84mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.84mM);ClearsolutionBIOLOGICALACTIVITY?物活性Larotrectinib(LOXO-101)?種ATP競爭性的、?服選擇性抑制劑，對原肌凝蛋?相關激酶(TRK)家族受體的三個亞型(TRKA，B和C)具有納爾級別的50%抑制濃度。IC50&TargetTrkATrkBTrkC體外研究Larotrectinib(LOXO-101)isanATP-competitiveoralinhibitorofthetropomyosin-relatedkinase(TRK)familyofreceptorkinases(TRKA,B,andC),withlownanomolar50%inhibitoryconcentrationsagainstallthreeisoforms,and1,000-foldorgreaterselectivityrelativetootherkinases[1][2].MeasurementofproliferationfollowingtreatmentwithLarotrectinib(LOXO-101)demonstratesadose-dependentinhibitionofcellproliferationinallthreecelllines.TheIC50islessthan100nMforCUTO-3.29andlessthan10nMforKM12andMO-91consistentwiththeknownpotencyofthisdrugfortheTRKkinasefamily[3].體內研究Inratandmonkeystudies,Larotrectinib(LOXO-101)demonstrates33-100%oralbioavailabilityand60-65%plasmaproteinbinding.Ithaslowbrainpenetration,andiswelltoleratedin28day(d)GLPtoxicologystudies.Asingledose(30mg/kg)ofLarotrectinib(LOXO-101)reducestyrosinephosphorylationofTRKAanddownstreamsignaltransduction(pERK)inthetumor>80%[1].AthymicnudemiceinjectedwithKM12cellsaretreatedwithLarotrectinib(LOXO-101)orallydailyfor2weeks.Dose-dependenttumorinhibitionisobserveddemonstratingtheabilityofthisselectivecompoundtoinhibittumorgrowthinvivo[4].Larotrectinib(LOXO-101)(200mg/kg/dayp.oforsixweeks)reducesleukemicinfiltrationtoundetectablelevelsinthebonemarrowandspleencomparedtovehicle-treatedmice.MicetreatedwithLarotrectinib(LOXO-101)arestillaliveandleukemia-freefourweeksafterthecessationoftreatment,asdeterminedbyXenogenimaging[5].PROTOCOLAnimalMice[4]Administration[4]Athymicnudemiceareusedthroughoutthestudy.5×105KM12cellsareinjectedsubcutaneouslyintothedorsalflankareaofthemice.Tumorvolumeismonitoredbydirectmeasurementwithcalipersandcalculatedbytheformula:length×(width2)/2.Followingtheestablishmentoftumorandwhenthetumorsizeisbetween150-200mm2,micearerandomlyselectedtoreceivediluent,60mg/kg/doseor200mg/kg/doseofLarotrectinib(LOXO-101).Larotrectinib(LOXO-101)isadministeredbyoralgavageoncedailyfor14days.Afterthelastdose,tissueandbloodarecollectedat3,6and24hourspost-treatment[4].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產品發(fā)表的科研?獻2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?MolOncol.2022Oct1.?EurJMedChem.2020Aug30;207:112744.?MolCancerTher.2021Oct8;molcanther.MCT-21-0632-A.2021.?JAnalSciTechnol.2020Jun.?bioRxiv.04Nov2021.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DoebeleRC,etal.AnOncogenicNTRKFusioninaPatientwithSoft-TissueSarcomawithResponsetotheTropomyosin-RelatedKinaseInhibitorLOXO-101.CancerDiscov.2015Oct;5(10):1049-57.[2].KarynBouhana,etal.LOXO-101,apanTRKinhibitor,ForTheTreatmentOfTRK-drivenCancers.[3].NagasubramanianR,etal.InfantileFibrosarcomaWithNTRK3-ETV6FusionSuccessfullyTreatedWiththeTropomyosin-RelatedKinaseInhibitorLOXO-101.PediatrBloodCancer.2016Aug;63(8):1468-70.[4].KathrynG,etal.GeneticModelingandTherapeuticTargetingofETV6-NTRK3withLoxo-101inAcuteLymphoblasticLeukemia