GDC-0276-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGDC-0276Cat.No.:HY-114237CASNo.:1494581-70-2分⼦式:C₂₄H₃₁FN₂O₄S分⼦量:462.58作⽤靶点:SodiumChannel作⽤通路:MembraneTransporter/IonChannel储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(270.22mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.1618mL10.8089mL21.6179mL5mM0.4324mL2.1618mL4.3236mL10mM0.2162mL1.0809mL2.1618mL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>>90%cornoilSolubility:≥6.25mg/mL(13.51mM);Clearsolution1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性GDC-0276⼀种有效的、选择性的、可逆的具有⼝服活性NaV1.7抑制剂，其IC50值为0.4nM。GDC-0276耐受性良好，显现良好的药代动⼒学特征。GDC-0276可⽤于疼痛以及解决现有⽌痛药物缺陷，如成瘾和脱靶副作⽤的相关研究。IC50&TargetIC50:0.4nM(NaV1.7Electrophysiology)[1]体内研究GDC-0276(oraladminstration;0.5-5mg/kg)showsenrichmentof14Cwithobservedspecificactivitiesof22.6µCi/mg.GDC-0276isnotdetectedinurine;however,metabolitesinurinewereenrichedin14Cwithobservedspecificactivitiesof19.6µCi/mg[3].AnimalModel:Sixdrug-naïvebeagledogsGroup1fourdogs(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