SAR405-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESAR405Cat.No.:HY-12481CASNo.:1523406-39-4分?式:C??H??ClF?N?O?分?量:443.85作?靶點(diǎn):PI3K;Autophagy作?通路:PI3K/Akt/mTOR;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥27mg/mL(60.83mM)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.2530mL11.2651mL22.5301mL5mM0.4506mL2.2530mL4.5060mL10mM0.2253mL1.1265mL2.2530mL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(chǔ)備液；?旦配成溶液，請分裝保存，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。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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)1/3MasterofBioactiveMolecules—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(5.63mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.63mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.63mM);Clearsolution4.請依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.63mM);ClearsolutionBIOLOGICALACTIVITY?物活性SAR405?創(chuàng)的，選擇性的，具有ATP競爭性的PI3KIII(PIK3C3)亞型Vps34抑制劑(IC50=1.2nM;Kd=1.5nM)。SAR405抑制饑餓或mTOR抑制誘導(dǎo)的?噬。具有抗癌活性[1][2]。IC50&TargetVps34Vps34Autophagy1.2nM(IC50)1.5nM(Kd)體外研究TheactivityofSAR405isnextevaluatedonadedicatedVps34cellularassayusingaGFP-FYVE–transfectedHeLacellline[1].SAR405preventsautophagyandsynergizeswithmTORinhibitionintumorcells.SAR405preventsautophagosomeformationwithanIC50of42nM.TreatmentofstarvedcellswithSAR405completelyinhibitstheconversiontoLC3-IIinadose-dependentmanner.TheeffectofSAR405onautophagyistheninvestigated.TheGFP-LC3modelisusedfortheHTSandconfirmeditsactivityonstarvedcells(IC50=419nM).TheconversionofLC3-IintoLC3-IIisalsoanalyzedbywesternblottingonwild-typeHeLaandH1299cells[2].PROTOCOLKinaseAssay[1]KiNativprofilingisperformed.Jurkatcelllysatesaretreatedwith1μMofSAR405.After15-minincubation,thedesthiobiotin-ATP-acylphosphateprobeisaddedandincubatedfor10min.SamplesarepreparedfortargetedMSanalysis.Briefly,samplesarepreparedfortrypsindigestion(denatureandthenreducealkylate)anddigestedwithtrypsin,anddesthiobiotinylatedpeptidesareenrichedonstreptavidinresin.Enrichedprobe-labeledpeptidesareanalyzedbyLCtandemMSonaThermo-LTQiontrapmassspectrometerusingproprietarydatacollectionmethodology.AllquantificationisperformedbyextractingcharacteristicfragmentionsignalsfromtargetedMS/MSspectraandcomparingsignalsincontrolandtreatedsamples[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatGenet.2021Apr;53(4):435-444.?CellMolImmunol.2021Aug;18(8):2024-2039.?MolCell.2021Mar18;81(6):1337-1354.e8.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE?NatCommun.2021Feb26;12(1):1322.?NatCommun.2020Aug13;11(1):4051.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].RonanB,etal.AhighlypotentandselectiveVps34inhibitoraltersvesicletraffickingandautophagy.NatChemBiol.2014Dec;10(12):1013-9.[2].PasquierB.SAR405,aPIK3C3/Vps34inhibitorthatpreventsautophagyandsynergizeswithMTORinhibitionintumorcells.Autophagy.2015Apr3;11(4):725-6.McePdfHeightCaution:Prod