GSK3186899-DDD-853651-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEGSK3186899Cat.No.:HY-112622CASNo.:1972617-87-0Synonyms:DDD-853651分⼦式:C₁₉H₂₈F₃N₇O₃S分⼦量:491.53作⽤靶点:Parasite作⽤通路:Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:250mg/mL(508.62mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0345mL10.1723mL20.3446mL5mM0.4069mL2.0345mL4.0689mL10mM0.2034mL1.0172mL2.0345mL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%saline1/2MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.23mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.23mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.23mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性GSK3186899(DDD-853651)CRK12的⼀个抑制剂，其对L.donovani的EC50值为1.4μM。IC50&TargetCRK12[1].体外研究GSK3186899(Compound7)isactiveagainstL.donovaniinanintra-macrophageassaywithanEC50valueof1.4μM,andshowsgoodselectivityagainstmammalianTHP-1hostcells(EC50value>50μM).ThisisnotaspotentasreporteddataforamphotericinB(EC50valueof0.07μMintheintra-macrophageassay),butiscomparabletotheclinicallyuseddrugsmiltefosineandparomomycin(EC50valuesof0.9μMand6.6μM,respectively).GSK3186899isalsoactiveincidalaxenicamastigoteassay(EC50valueof0.1μM).Ataconcentrationof0.2μM,GSK3186899iscytocidalat96h;increasingtheconcentrationto1.8μMreducedthistimeto48h.GSK3186899demonstratesalessthan10-foldvariationinpotencyagainstapanelofLeishmania-derivedlines.GSK3186899isalsomoreactiveinapanelofLeishmanialinesusinghumanperipheralbloodmononuclearcellsasthehostcells[1].体内研究Inthemousemodelofinfection,GSK3186899demonstratescomparableactivitytothefront-linedrugmiltefosine,reducingparasitelevelsby99%whendosedorallytwiceadayfor10daysat25mg/kg.Theefficacyoftreatmentisdependentondose,frequency,andduration(10daysbetterthan5).Thenon-clinicalsafetydataforGSK3186899suggestsasuitabletherapeuticwindowforprogressionintoregulatorypreclinicalstudies.Non-GLPpreclinicalassessmentofcardiovasculareffectsandgenotoxicitydoesnotrevealanyissuesthatwouldpreventfurtherdevelopment.Inaddition,therearenonotableadverseeffectsinaratseven-dayrepeat-doseoraltoxicitystudywithrespecttoclinicalchemistryandhistopathologyatalldosestested.BoththeinvivoefficacyandsafetyprofileofGSK3186899supportprogressiontodefinitivesafetystudies[1].REFERENCES[1].WyllieS,etal.Cyclin-dependentkinase12isadrugtargetforvisceralleishmaniasis.Nature.2018Aug;560(7717):192-197.McePdfHeightCaution:Producthasnotbeenfullyval