GSK2982772-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEGSK2982772Cat.No.:HY-101760CASNo.:1622848-92-3分?式:C??H??N?O?分?量:377.4作?靶點(diǎn):RIPkinase作?通路:Apoptosis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:250mg/mL(662.43mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.6497mL13.2485mL26.4971mL5mM0.5299mL2.6497mL5.2994mL10mM0.2650mL1.3249mL2.6497mL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(chǔ)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(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(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>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(5.51mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(5.51mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.62mM);ClearsolutionBIOLOGICALACTIVITY?物活性GSK2982772可?服的、有效的ATP競爭型的RIP1酶抑制劑，對?和猴?RIP1的IC50值分別為16nM和20nM。IC50&TargetIC50:16nM(humanRIP1FP)IC50:20nM(monkeyRIP1FP)IC50:2μM(ratRIP1FP)IC50:2.5μM(mouseRIP1FP)[1]體外研究GSK2982772showsmorethan1,000-foldselectivityforERK5overapanelofover339kinasesat10μM.Instimulatedcellularsystems,GSK2982772isalsoabletoreducespontaneousproductionofcytokines(IL-1βandIL-6)inaconcentration-dependentfashionfromulcerativecolitisexplanttissueinovernightincubations.GSK2982772producesaweakconcentrationdependentinhibitionofhERGinhumanembryonickidney(HEK-293)cells,withanestimatedIC50of195μM,andalsoshowsaweakactivationofthehumanPregnaneXreceptor(hPXR)withanEC50of13μM[1].體內(nèi)研究GSK2982772isdosedorally15minpriortoTNFandshows68,80,and87%protectionfromtemperaturelossover6h,atdosesof3,10,and50mg/kg,respectively.InthecorrespondingTNF/zVADmodel,GSK2982772shows13,63,and93%protectionfromtemperaturelossover3h.GSK2982772displaysagoodfreefractioninbloodinrats(4.2%),dogs(11%),cynomolgusmonkeys(11%),andhumans(7.4%).Theinhibitorhasagoodpharmacokineticprofileacrossbothratsandmonkeys.GSK2982772distributesintoarangeoftissuesincludingthecolon,liver,kidney,andheartatconcentrationscomparabletothoseofblood.However,GSK2982772haslowbrainpenetrationinrat(4%)despitepossessinggoodcellpermeability(21×10-6cm/s)[1].PROTOCOLAnimalMice:Atotalof7miceperdosegroupareorallypredosedwithsalineorGSK2982772atdosesof3,10,andAdministration[1]50mg/kg15minbeforei.v.administrationofmouseTNF(30μg/mouse).Temperaturelossinthemiceismeasuredbyarectalprobe.Thestudyisterminatedafter6hwhenthecontrolgrouplost7°C[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?BiochemPharmacol.2020Feb;172:113751.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].HarrisPA,etal.DiscoveryofaFirst-in-ClassReceptorInteractingProtein1(RIP1)KinaseSpecificClinicalCandidate(GSK2982772)fortheTreatmentofInflammatoryDiseases.JMedChem.2017Feb23;60(4):1247-1261.McePdfHeightCaution:Productha