GSK2193874-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEGSK2193874Cat.No.:HY-100720CASNo.:1336960-13-4分?式:C??H??BrF?N?O分?量:691.62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(144.59mM;Needultrasonic)掃描?維碼，H2O:<0.1mg/mL(insoluble)運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.4459mL7.2294mL14.4588mL5mM0.2892mL1.4459mL2.8918mL10mM0.1446mL0.7229mL1.4459mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.08mg/mL(3.01mM);Clearsolution此?案可獲得≥2.08mg/mL(3.01mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/3www.MedChemEwww.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.08mg/mL(3.01mM);Clearsolution此?案可獲得≥2.08mg/mL(3.01mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。3.以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。請(qǐng)依序添加每種溶劑：5%DMSO95%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(3.61mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性GSK2193874具有?服活性的有效的選擇性TRPV4拮抗劑，作?于rTRPV4和hTRPV4，IC50分別為2nM和40nM。IC50&TargetIC50:2nM(rTRPV4),40nM(hTRPV4)[1]體外研究GSK2193874isprofiledagainstTRPchannelsandisselectiveagainstTRPV1,TRPA1,TRPC3,TRPC6,andTRPM8(IC50>25μM)[1].GSK2193874isaselective,orallyactiveTRPV4blockerthatinhibitsCa2+influxthroughrecombinantTRPV4channelsandnativeendothelialTRPV4currents.Inwhole-cellpatch-clampstudies,GSK2193874inhibitsactivationofrecombinantTRPV4currentswhenappliedtotheextracellularsolutionat3nMandabovebutisineffectiveatupto10μMwhenappliedtotheinsideofthecellbyinclusionintheintracellularpipettesolution[2].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3www.MedChemEwww.MedChemE?Autophagy.2021Feb25;1-15.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].CheungM,etal.DiscoveryofGSK2193874:AnOrallyActive,Potent,andSelectiveBlockerofTransientReceptorPotentialVanilloid4.ACSMedChemLett.2017Mar20;8(5):549-554.[2].ThorneloeKS,etal.AnorallyactiveTRPV4channelblockerpreventsandresolvespulmonaryedemainducedbyheartfailure.SciTranslMed.2012Nov7;4(159):159ra148.McePdfHeight關(guān)注MCE中國(guó)公眾號(hào)，

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