Ensartinib-dihydrochloride-X-396-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpressVIP

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEnsartinibdihydrochlorideCat.No.:HY-103714ACASNo.:2137030-98-7Synonyms:X-396dihydrochloride分?式:C??H??Cl?FN?O?分?量:634.36作?靶點(diǎn):Anaplasticlymphomakinase(ALK);c-Met/HGFR作?通路:ProteinTyrosineKinase/RTK儲(chǔ)存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:35.71mg/mL(56.29mM;Needultrasonic)H2O:33.33mg/mL(52.54mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.5764mL7.8820mL15.7639mL5mM0.3153mL1.5764mL3.1528mL10mM0.1576mL0.7882mL1.5764mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(3.28mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(3.28mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.28mM);Clearsolution4.請(qǐng)依序添加每種溶劑：PBSSolubility:14.29mg/mL(22.53mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Ensartinibdihydrochloride(X-396dihydrochloride)?種有效的雙重的ALK/MET抑制劑，IC50分別<0.4nM和0.74nM。IC50&TargetIC50:[1]體外研究Ensartinib(X-396)dihydrochlorideisapotentanddualALK/METinhibitorwithIC50sofEML4-ALKE13;A20(IC50:15nM).EnsartinibdihydrochlorideisalsopotentinH2228lungcancercellsharboringEML4-ALKE6a/b;A20(IC50:45nM).Furthermore,X-376ispotentinSUDHL-1lymphomacellsharboringNPM-ALK(IC50:9nM)[1].體內(nèi)研究Ensartinib(X-396)dihydrochlorideshowssubstantialbioavailabilityandmoderatehalf-livesinvivo.NudemiceharboringH3122xenograftsaretreatedwithEnsartinibdihydrochlorideat25mg/kgbid.Ensartinibdihydrochloridesignificantlydelaysthegrowthoftumorscomparedtovehiclealone.Inthexenograftexperiments,Ensartinibdihydrochlorideappearswell-toleratedinvivo.MouseweightisunaffectedbyEnsartinibdihydrochloridetreatment.Drug-treatedmiceappearhealthyanddonotdisplayanysignsofcompoundrelatedtoxicity.TofurtherassesspotentialsideeffectsofEnsartinibdihydrochloride,additionalsystemictoxicityandtoxico-kineticstudiesareperformedinSpragueDawley(SD)rats.Following10daysofrepeatedoraladministrationofEnsartinibdihydrochlorideat20,40,80mg/kginSDrats,allanimalssurvivetostudytermination.Thenosignificanttoxicity(NST)levelsaredeterminedtobe80mg/kgforEnsartinibdihydrochloride.AtNSTlevels,EnsartinibdihydrochlorideachievesanAUCof66μM×hrandaCmaxof7.19μM[1].PROTOCOLCellAssay[1]Forviabilityexperiments,cellsareseededin96-wellplatesat25%-33%confluencyandexposedtodrugs.ThehumanlungadenocarcinomacelllinesH3122andH2228aretreatedwithEnsartinib(10,30,100,300and1000nM).SUDHL-1lymphomacellsaretreatedwithEnsartinib(5,10,30,100and300nM).SY5YneuroblastomacellsaretreatedwithEnsartinib(30,100,300and1000nM).At72hourspostEnsartinibaddition,CellTiterBlueReagentisaddedandfluorescenceismeasuredonaSpectramaxspectrophotometer.Allexperimentalpointsaresetupinhextuplicatereplicatesandareperformedatleasttwoindependenttimes.IC50sarecalculatedusingGraphPadPrismversion5forWindows.Thecurvesarefitusinganonlinearregressionmodelwithalog(inhibitor)vs.responseformula[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Nudemice(nu/nu)areinjectedwithH3122cells.Oncetumorsreachanaveragevolumeof450mm3,atotalof27athymicmiceharboringH3122tumorsarerandomizedanddosedviaoralgavagewith25mg/kgEnsartiniborthecontrolvehicle.Two,five,andfifteenhoursafterthesingletreatment(3tumors/timepoint/group),micearesacrificedandserumiscollectedforassessmentofdrugconcentrationusinganLC-MSbasedbioanalyticalmethod[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Cancers.2020Mar28;12(4):813.?DrugDesDevTher.2020Nov30;14:5259-5273.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LovlyCM,etal.InsightsintoALK-drivencancersrevealedthroughdevelopmentofnovelALKtyrosinekinaseinhibitors.Cance