Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGDC-0276Cat.No.:HY-114237CASNo.:1494581-70-2分?式:C??H??FN?O?S分?量:462.58作?靶點:SodiumChannel作?通路:MembraneTransporter/IonChannel儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:125mg/mL(270.22mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1618mL10.8089mL21.6179mL5mM0.4324mL2.1618mL4.3236mL10mM0.2162mL1.0809mL2.1618mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥6.25mg/mL(13.51mM);Clearsolution1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEBIOLOGICALACTIVITY?物活性GDC-0276?種有效的、選擇性的、可逆的具有?服活性NaV1.7抑制劑，其IC50值為0.4nM。GDC-0276耐受性良好，顯現(xiàn)良好的藥代動?學(xué)特征。GDC-0276可?于疼痛以及解決現(xiàn)有?痛藥物缺陷，如成癮和脫靶副作?的相關(guān)研究。IC50&TargetIC50:0.4nM(NaV1.7Electrophysiology)[1]體內(nèi)研究GDC-0276(oraladminstration;0.5-5mg/kg)showsenrichmentof14Cwithobservedspecificactivitiesof22.6μCi/mg.GDC-0276isnotdetectedinurine;however,metabolitesinurinewereenrichedin14Cwithobservedspecificactivitiesof19.6μCi/mg[3].AnimalModel:Sixdrug-na?vebeagledogsGroup1fourdogs(n=2persex)andGroup22BDCdogs(n=2male)[3]Dosage:0.5,1,2,3,4,5mg/kgAdministration:OraladminstrationResult:Showedmeanspecificactivitiesof12.2μCi/mg(a24%enrichment)(n=4animals)and23.5μCi/mg(a139%enrichment)(n=2animals)forGroups1and2,respectively.REFERENCES[1].RothenbergME,etal.Safety,Tolerability,andPharmacokineticsofGDC-0276,aNovelNaV1.7Inhibitor,inaFirst-in-Human,Single-andMultiple-DoseStudyi[2].StevenJ.McKerrall,etal.Nav1.7inhibitorsforthetreatmentofchronicpain.Bioorganic&MedicinalChemistryLetters(2018)[3].TakahashiRH,etal.UnequalAbsorptionofRadiolabeledandNonradiolabeledDrugfromtheOralDoseLeadstoIncorrectEstimatesofDrugAbsorptionandCirculatingMetabolitesinaMassBalanceStudy.DrugMetabLett.2019;13(1):37-44.McePdfHeightCaution:Producthasnotbeenfullyvalidatedformedicalapplications.Forresearch