Navtemadlin-AMG-232-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENavtemadlinCat.No.:HY-12296CASNo.:1352066-68-2Synonyms:AMG232;KRT-232分?式:C??H??Cl?NO?S分?量:568.55作?靶點(diǎn):MDM-2/p53;E1/E2/E3Enzyme作?通路:Apoptosis;MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2years*該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?。溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥50mg/mL(87.94mM)H2O:≥0.1mg/mL(0.18mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.7589mL8.7943mL17.5886mL5mM0.3518mL1.7589mL3.5177mL10mM0.1759mL0.8794mL1.7589mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液；該產(chǎn)品在溶液狀態(tài)不穩(wěn)定，建議您現(xiàn)?現(xiàn)配，即刻使?.體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?式選擇適當(dāng)?shù)娜芙?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(shí)驗(yàn)結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，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:≥2.5mg/mL(4.40mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.40mM);Clearsolution3.請依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(4.40mM);Clearsolution4.請依序添加每種溶劑：50%PEG300>>50%salineSolubility:10mg/mL(17.59mM);Suspendedsolution;Needultrasonic5.請依序添加每種溶劑：PBSSolubility:1.5mg/mL(2.64mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Navtemadlin(AMG232)?種有效，選擇性，可?服的p53-MDM2相互作?抑制劑，IC50值為0.6nM，與MDM2結(jié)合的Kd為0.045nM。IC50&TargetIC50:0.6nM(p53-MDM2interaction)[1]Kd:0.045nM(MDM2)[1]體外研究Navtemadlin(AMG232)(10μM)inducesp53signalingandinhibitstumorcellproliferationinthreep53wild-typetumorcelllines[1].Navtemadlinpotentlyinhibitsproliferationofnon-MDM2-amplifiedHCT116colorectalcells(IC50=10nM)[3].CellViabilityAssay[1]CellLine:SJSA-1,HCT116,ACHN,NCI-H460,MOLM-13,RKO,MCF7,22RV1,HT-29,PC-3,NCI-H82,NCI-SNU1,MG-63,NCI-H2452,SW982,C32,SK-HEP-1,A375,RT4,RPMI2650,MDA-MB-134-VI,NCI-H2347andA427cells.Concentration:0-10μM.IncubationTime:72hours.Result:Inducedp53signalingandinhibitstumorcellproliferationinthreep53wild-typetumorcelllines(SJSA-1,HCT116,andACHN).Causedrobustp21mRNAinductionbetween9.76and34.9foldwithIC50valuesrangingfrom12.8to46.8nM.體內(nèi)研究Navtemadlin(AMG232)(10,25,75mg/kg,oncedaily,p.o.)activatesp53pathwayactivityinvivo[1].Navtemadlin(10,25,75mg/kg,oncedaily,p.o.)potentlyinhibitsgrowthoftumorxenograftsinmice[1].Navtemadlin(10,25,75mg/kg,oncedaily,p.o.)blocksDNAsynthesisandinducesapoptosisinvivo[1].Navtemadlincausesadose-dependenttumorgrowthinhibitionwithanED50of16mg/kg[2].AnimalModel:Femaleathymicnudemice(n=10/group)basedcancermodels[1].2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEDosage:10,25,75mg/kg.Administration:Oncedailybyoralgavage.Result:Resultedinsignificanttumorgrowthinhibitionacrossallmodels.SJSA-1,anMDM2amplifiedosteosarcomamodel,wasthemostsensitivetoAMG232treatmentwithanED50of9.1mg/kg.Inthehighestdosegroupof75mg/kg,10/10tumorscompletelyregressedandwereundetectableafter10daysoftreatment.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ClinTranslMed.2022Jul;12(7):e961.?BMCBiol.2017Nov9;15(1):108.?CellDeathDiscov.2020Jul6;6:57.?Biomedicines.2022,10(3),638.?ClinExpDermatol.2022May6.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CanonJ,etal.TheMDM2InhibitorAMG232DemonstratesRobustAntitumorEfficacyandPotentiatestheActivityofp53-InducingCytotoxicAgents.MolCancerTher.2015Mar;14(3):649-58.[2].RewY,etal.DiscoveryofasmallmoleculeMDM2inhibitor(AMG232)fortreatingcancer.JMedChem.2014Aug14;57(15):6332-41.McePdfHeightCaution