AMG9810-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAMG9810Cat.No.:HY-101736CASNo.:545395-94-6分⼦式:C₂₁H₂₃NO₃分⼦量:337.41作⽤靶点:TRPChannel作⽤通路:MembraneTransporter/IonChannel;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥33mg/mL(97.80mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.9638mL14.8188mL29.6375mL5mM0.5928mL2.9638mL5.9275mL10mM0.2964mL1.4819mL2.9638mL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.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(7.41mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.41mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.41mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性AMG9810选择性和竞争性的⾹草素受体1(TRPV1)拮抗剂，对⼈类和⼤⿏TRPV1的IC50值分别为24.5和85.6nM。IC50&TargetIC50:24.5nM(humanTRPV1),85.6nM(ratTRPV1)[1]体外研究AMG9810isacompetitiveantagonistofcapsaicinactivation(IC50valueforhumanTRPV1,24.5±15.7nM;ratTRPV1,85.6±39.4nM)andblocksallknownmodesofTRPV1activation,includingprotons(IC50valueforratTRPV1,294±192nM;humanTRPV1,92.7±72.8nM),heat(IC50valueforratTRPV1,21±17nM;humanTRPV1,15.8±10.8nM),andendogenousligands,suchasanandamide,N-arachidonyldopamine,andoleoyldopamine.AMG9810blockscapsaicin-evokeddepolarizationandcalcitoningene-relatedpeptidereleaseinculturesofratdorsalrootganglionprimaryneurons.AMG9810inhibitscapsaicin-,proton-,heat-,andendogenousligand-induceduptakeof45Ca2+intoTRPV1-expressingcells[1].体内研究AMG9810iseffectiveatpreventingcapsaicin-inducedeyewipinginadose-dependentmanner,anditreversesthermalandmechanicalhyperalgesiainamodelofinflammatorypaininducedbyintraplantarinjectionofcompleteFreund'sadjuvant.Ateffectivedoses,AMG9810doesnotshowanysignificanteffectsonmotorfunction.AMG9810isthefirstcinnamideTRPV1antagonistreportedtoblockcapsaicin-inducedeyewipingbehaviorandreversehyperalgesiainananimalmodelofinflammatorypain[1].AMG9810,promotesmouseskintumordevelopment.ThetopicalapplicationofAMG9810resultsinasignificantincreaseintheexpressionleveloftheepidermalgrowthfactorreceptor(EGFR)anditsdownstreamAkt/mammaliantargetofrapamycin(mTOR)-signalingpathway[2].PROTOCOLKinaseAssay[1]Culturedadultratdorsalrootganglianeuronsin96-wellplatesarewashedtwicewithreleasebuffertoinitiatetheassay.CGRPreleaseisinducedbyincubationofneuronswithcapsaicinfor10minatroomtemperature.TheculturesarepreincubatedwithincreasingconcentrationsofcapsazepineorAMG9810for15min,followedby300nMcapsaicinactivationfor10minatroomtemperature.TheextracellularmediumiscollectedandtheCGRPcontentisdeterminedusingacommerciallykit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[2]ToassesscyotoxicityofAMG9810,N/TERT1cellsaretreatedwithdifferentconcentrationsofAMG9810(0.25,0.5,1,5μM)andculturedforvariousperiodsoftime(24,48,72h).TheCellTiter96AQueousOneSolutionisaddedtoeachwellandthencellsarekeptina37°C,5%CO2incubatorfor1h.Absorbanceis2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEthenmeasuredat492and690nmwithaplatereader[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats:AMG9810isdissolvedinDMSO.Ratsareacclimatedfor30to45minina30×30×30-cmPlexiglasAdministration[1]chambersbeforetheintraperitonealinjectionofeithervehicle(DMSO)orAMG9810.Injectionsaremadeovera5-speriodinthelowerrightventralquadrantoftheabdomeneither15,30,or60minbeforeintraocularapplicationofcapsaicin.Intraocularapplicationofcapsaicin(3μg/20μLin10%ethanol/PBS)orvehicle(20μLin10%ethanol/PBS)isdonewithapipette,andthenumberoffrontpaweyewipesiscountedovera5-minperiodin1-minintervals[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•StemCellRevRep.2021Jun;17(3):999-1013.•JBiolChem.2021May19;100806.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GavvaNR,etal.AMG9810[(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide],anovelvanilloidreceptor1(TRPV1)antagonistwithantihyperalgesicproperties.JPharmacolExpTher.2005Apr;313(1):474-84.[2].LiS,etal.TRPV1-antagonistAMG9810promotesmouseskintumorigenesisthroughEGFR/Ak