AMG9810-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAMG9810Cat.No.:HY-101736CASNo.:545395-94-6分?式:C??H??NO?分?量:337.41作?靶點(diǎn):TRPChannel作?通路:MembraneTransporter/IonChannel;NeuronalSignaling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:≥33mg/mL(97.80mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9638mL14.8188mL29.6375mL5mM0.5928mL2.9638mL5.9275mL10mM0.2964mL1.4819mL2.9638mL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。-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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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:≥2.5mg/mL(7.41mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.41mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(7.41mM);ClearsolutionBIOLOGICALACTIVITY?物活性AMG9810選擇性和競(jìng)爭(zhēng)性的?草素受體1(TRPV1)拮抗劑，對(duì)?類(lèi)和??TRPV1的IC50值分別為24.5和85.6nM。IC50&TargetIC50:24.5nM(humanTRPV1),85.6nM(ratTRPV1)[1]體外研究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].體內(nèi)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?邊的抑制劑?師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.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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