GSK2193874-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK2193874Cat.No.:HY-100720CASNo.:1336960-13-4分⼦式:C₃₇H₃₈BrF₃N₄O分⼦量:691.62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:100mg/mL(144.59mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.4459mL7.2294mL14.4588mL5mM0.2892mL1.4459mL2.8918mL10mM0.1446mL0.7229mL1.4459mL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%salineSolubility:≥2.08mg/mL(3.01mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.01mM);Clearsolution3.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(3.61mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性GSK2193874具有⼝服活性的有效的选择性TRPV4拮抗剂，作⽤于rTRPV4和hTRPV4，IC50分别为2nM和40nM。IC50&TargetIC50:2nM(rTRPV4),40nM(hTRPV4)[1]体外研究GSK2193874isprofiledagainstTRPchannelsandisselectiveagainstTRPV1,TRPA1,TRPC3,TRPC6,andTRPM8(IC50>25μM)[1].GSK2193874isaselective,orallyactiveTRPV4blockerthatinhibitsCa2+influxthroughrecombinantTRPV4channelsandnativeendothelialTRPV4currents.Inwhole-cellpatch-clampstudies,GSK2193874inhibitsactivationofrecombinantTRPV4currentswhenappliedtotheextracellularsolutionat3nMandabovebutisineffectiveatupto10μMwhenappliedtotheinsideofthecellbyinclusionintheintracellularpipettesolution[2].体内研究Thepharmacokinetic(PK)propertiesforGSK2193874areevaluatedinbothratanddogandfoundtohavehalf-livesandoralexposuresuitablefororaldosinginchronicanimalmodels(RatPK:ivCL=7.3mL/min/kg,pot1/2=10h,%F=31.DogPK:ivCL=6.9mL/min/kg,pot1/2=31h,%F=53).Inaddition,GSK2193874showsnobloodpressureorheartrateeffectinratswhendoseupto30mg/kg.GSK2193874isthefirst-in-classorallybioavailableTRPV4inhibitorthatdemonstratedabilitytoimprovepulmonaryfunctionsinanumberofheartfailuremodels[1].GSK2193874showslowclearance(7.3mL/min/kg)andgoodratoralbioavailability(31%)[2].PROTOCOLAnimalRats[2]Administration[2]AdultmaleSprague-Dawleyrats(n=7to8pergroup)aretreatedwithvehicle(6%Cavitron)orGSK2193874(30mg/kgperday)viaoralgavageforatleast4daysbeforeosmoticchallenges.Ratsundergoacuteandchronichyper-andhypo-osmoticchallenges.Sprague-Dawleyratsareadministeredvehicle(0.9%NaCl,25mL/kg),NSC269420(30mg/kg),orhydrochlorothiazide(30mg/kg)viaoralgavage.Urineisthencollectedover4hoursfollowedbybloodsampling.Ratsrecoverfor4daysandthenreceiveGSK2193874(30mg/kgperdayoralgavage)for5daysbeforerepeatingthediureticchallenge.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Autophagy.2021Nov;17(11):3592-3606.•JNanobiotechnology.2022Jul6;20(1):314.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•ActaPharmacolSin.2022Sep23.•CellCalcium.2022Jun;104:102590.•JEthnopharmacol.2022Feb11;290:115105.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CheungM,etal.DiscoveryofGSK2193874:AnOrallyActive,Potent,andSelectiveBlockerofTransientReceptorPotentialVanilloid4.ACSMedChemLett.2017Mar20;8(5):549-554.[2].ThorneloeKS,etal.AnorallyactiveTRPV4channelblockerpreventsandresolvespulmonaryedemainducedbyheartfailure.SciTranslMed.2012Nov7;4(159):159ra148.McePdfHeig