SB-705498-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemESB-705498Cat.No.:HY-10633CASNo.:501951-42-4分?式:C??H??BrF?N?O分?量:429.23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:100mg/mL(232.98mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3298mL11.6488mL23.2975mL5mM0.4660mL2.3298mL4.6595mL10mM0.2330mL1.1649mL2.3298mL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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:2.5mg/mL(5.82mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.82mM);ClearsolutionBIOLOGICALACTIVITY?物活性SB-705498?種有效的，選擇性的，可?服的TRPV1拮抗劑，pIC50值為7.1。IC50&TargetpIC50:7.1體外研究SB705498(0.3nM-1μM)potentlyinhibitscapsaicin-inducedactivationofhumanTRPV1expressedin1321N1cellsorHEK293cellswithapparentpKiof7.5or7.6,respectively.Coapplicationof100nMSB705498rapidly,completelyandreversiblyinhibitshTRPV1expressedinHEK293cells.SB705498hasnosignificanteffectonendogenous[Ca2+]responsesinHEK293cellsproducedbymuscarinicacetylcholinereceptoractivationwithcarbacholorstore-operatedchannel-mediatedCa2+entryafterdepletionofintracellularstoreswiththeCa2+pumpinhibitorthapsigargin.SB705498(10pM-1μM)alsohasnosignificantantagonisteffectversusthecloseTRPV1receptorparalogTRPV4transientlyexpressedinHEK293cellsandactivatedusingthesyntheticligand4α-phorbol-12,13-didecanoate(10μM).SB705498revealsgoodantagonistpotencyagainstboththeratandguineapigTRPV1.SB705498antagonizesratandguineapigTRPV1withpKiof7.5and7.3,respectively.Coapplicationof100nMto10μMSB705498tothesteadystateofamaintainedcapsaicinresponseleadstorapidandcompleteinhibitionofhTRPV1at-70mV.SB705498inhibitscapsaicin-mediatedactivationofhTRPV1withIC50of3nMand17nMatpositiveandnegativeholdingpotentials(-70mVand+70mV),respectively.Coapplicationof1μMSB705498totheplateauperiodoftheresponseproducescompleteandreversibleinhibitionoftheTRPV1-mediatedconductance[1].SB705498showsapproximatelyequalactivityversusmultipleanddiversechemicalandphysicalmodesofTRPV1receptoractivation.SB705498showslittleornoactivityversusawiderangeofionchannels,receptorsandenzymes.SB705498producesfullblockadeofheataswellaspHactivationof

hTRPV1[2].體內(nèi)研究SB705498exhibitspotentandreversibleblockadeagainstthemultiplemodesofTRPV1activation,namelythevanilloid(capsaicin),heat-andacid-mediatedactivationofthereceptor.SB705498displaysexcellentactivityat10and30mg/kgpowithgoodreversalofallodynia.SB705498(10mg/kgp.o.)gives80%reversalofallodyniaintheguineapigFCAmodel[2].戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JExpClinCancerRes.2020Oct2;39(1):206.?JBiolChem.2022May;298(5):101847.?SciRep.2016Jul20;6:30168.Seemorecustomervalidationsonwww.MedChemEREFERENCES2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE[1].MartinJ.Gunthorpe,etal.CharacterizationofSB-705498,aPotentandSelectiveVanilloidReceptor-1(VR1/TRPV1)AntagonistThatInhibitstheCapsaicin-,Acid-,andHeat-MediatedActivationoftheReceptor.JPETJune2007vol.321no.31183-1192.[2].RamiHK,etal.DiscoveryofSB-705498:apotent,selectiveandorallybioavailableTRPV1antagonistsuitableforclinicaldevelopment.BioorgMedChemLett.2006Jun15;16(12):3287-91.McePdfHeig