AT-533-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAT-533Cat.No.:HY-148877CASNo.:908112-37-8分⼦式:C₂₃H₃₀N₄O₃分⼦量:410.51作⽤靶点:HSP;HSV;HIF/HIFProlyl-Hydroxylase;VEGFR;NF-κB;ERK;Akt;FAK作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease;Anti-

infection;ProteinTyrosineKinase/RTK;NF-κB;MAPK/ERK

Pathway;StemCell/Wnt;PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:33.33mg/mL(81.19mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4360mL12.1800mL24.3599mL5mM0.4872mL2.4360mL4.8720mL10mM0.2436mL1.2180mL2.4360mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.5mg/mL(6.09mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.09mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.09mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AT-533⼀种有效的Hsp90和HSV抑制剂。AT-533通过阻断HIF-1α/VEGF/VEGFR-2信号通路抑制肿瘤⽣长和⾎管⽣成。AT-533还抑制下游通路的激活，包括Akt/mTOR/p70S6K,Erk1/2和FAK。AT-533抑制⼈脐静脉内⽪细胞(HUVEC)的管形成、细胞迁移和侵袭。IC50&TargetHSP90HSV-1ERK1ERK2NF-κBAktHIF-1αVEGF/VEGFR-2体外研究AT-533(0-1350nM;24hor48h)inhibits20ng/mLVEGF-inducedtubeformation,cellmigration,andinvasionofHUVECs[1].AT-533(2μMor75μM;24h)inhibitstheHIF-1α/VEGFsignalingpathwayinhypoxia-inducedbreastcancercells,aswellasinhibitingAkt/mTOR/p70S6K,Erk1/2,andFAKphosphorylation[1].AT-533(10nM,50nM;48h)showsanti-angiogenicabilityinchorioallantoicmembrane(CAM)model[1].AT-533(0.5μM;2h,4h)decreasesTNF-α,IL-1βandIL-6productioninRAW264.7andBV2cellsinducedbyHSV-1[2].CellViabilityAssay[1]CellLine:Humanumbilicalveinendothelialcells(HUVECs):MCF-7andMDA-MB-231Concentration:0,5.6,16.7,50,150,450,and1350nMIncubationTime:12h,24h,48h,and72hResult:Inhibitedcellviabilityat48hwithanIC50valueof50.1nM.WesternBlotAnalysis[1]CellLine:MCF-7cellsandMDA-MB-231cellsConcentration:5nM,10nM,50nM,and75nMIncubationTime:24hResult:InhibitedthephosphorylationofVEGF-2,Akt,mTOR,Erk1/2,FAK.体内研究AT-533(10mg/kg;i.p.;oncedailyfor21d)suppressestheexpressionoftheHIF-1α/VEGFsignaling2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEpathway-relatedproteinsinMDA-MB-231breastcancerxenograftstumormodelinmouse[1].AT-533(1,2and4mg/kg;i.p.;oncedailyfor30d)hasnomortality,lossofappetiteandbodyweight,adversereactionsinSprague-Dawleyratsinsubacutetoxicitytest[3].AnimalModel:MaleC57BL/6micewithMDA-MB-231breastcancerxenografts[1]Dosage:10mg/kg;Administration:Intraperitonealinjection;oncedailyfor21daysResult:SignificantlydownregulatedHIF-1αandVEGFexpression.REFERENCES[1].ZhangPC,etal.AT-533,anovelHsp90inhibitor,inhibitsbreastcancergrowthandHIF-1α/VEGF/VEGFR-2-mediatedangiogenesisinvitroandinvivo.BiochemPharmacol.2020Feb;172:113771.[2].LiF,etal.AT-533,aHsp90inhibitor,attenuatesHSV-1-inducedinflammation.BiochemPharmacol.2019Aug;166:82-92.[3].WuY,etal.SubacutetoxicologicalevaluationofAT-533andAT-533gelinSprague-Dawleyrats.ExpTherMed.2021Jun;21(6):632.McePdfHeightCaution:Pro