VRT-043198-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVRT-043198Cat.No.:HY-112226CASNo.:244133-31-1分?式:C??H??ClN?O?分?量:480.94作?靶點(diǎn):Caspase;DrugMetabolite作?通路:Apoptosis;MetabolicEnzyme/Protease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:180mg/mL(374.27mM;Needultrasonic)Methanol:12.5mg/mL(25.99mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.0793mL10.3963mL20.7926mL5mM0.4159mL2.0793mL4.1585mL10mM0.2079mL1.0396mL2.0793mL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；?旦配成溶液，請(qǐng)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(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:4.5mg/mL(9.36mM);Clearsolution;Needultrasonic2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥4.5mg/mL(9.36mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥4.5mg/mL(9.36mM);ClearsolutionBIOLOGICALACTIVITY?物活性VRT-043198VX-765(Belnacasan)的活性代謝物，有效的、選擇性的、能透過(guò)?腦屏障的caspase-1的抑制劑。VRT-043198對(duì)caspase-1和caspase-4的Ki值分別為0.8nM和0.6nM。IC50&TargetCaspase-1Caspase-40.8nM(Ki)0.6nM(Ki)體外研究VRT-043198exhibits100-to10,000-foldselectivityagainstothercaspase-3and-6to-9[1].VRT043198inhibitsthereleaseofinterleukin(IL)-1βandIL-18,butithaslittleeffectonthereleaseofseveralothercytokines,includingIL-1α,tumornecrosisfactor-,IL-6andIL-8.VRT-043198inhibitedIL-1βreleasefrombothPBMCs(n=8)andwholeblood(n=4)withIC50valuesof0.67±0.55and1.9±0.80nM,respectively[1].VRT-043198lackspotentantiapoptoticactivity[1].體內(nèi)研究VX-765isconvertedrapidlytoVRT-043198undertheactionofplasmaandliveresterasesandalsomuchmoreslowlyinaqueoussolution[1].VX765reducesdiseaseseverityandtheexpressionofinflammatorymediatorsinmodelsofrheumatoidarthritisandskininflammation[1].VX765(25,50,100,or200mg/kg)inhibitslipopolysaccharide-inducedcytokinesecretion[1].AnimalModel:Na?vemaleCD-1mice[1].Dosage:25-200mg/kg.Administration:Oralgavage1hbeforei.v.injectionof2mg/kgE.coliLPS(strain0111:B4).Result:ReducedserumIL-1βlevels.REFERENCES[1].WoodsWannamaker,etal.(S)-1-((S)-2-{[1-(4-amino-3-chloro-phenyl)-methanoyl]-amino}-3,3-dimethyl-butanoyl)-pyrrolidine-2-carboxylicacid((2R,3S)-2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-amide(VX-765),anorallyavailableselectiveinterleukin(IL)-convertingenzyme/caspase-1inhibitor,exhibitspotentanti-inflammatoryactivitiesbyinhibitingthereleaseofIL-1betaandIL-18.JPharmacolExpTher.2007May;321(2):509-16.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidatedfo