Voxelotor-GBT-440-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVoxelotorCat.No.:HY-18681CASNo.:1446321-46-5Synonyms:GBT440分?式:C??H??N?O?分?量:337.37作?靶點(diǎn):Others作?通路:Others儲(chǔ)存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(296.41mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9641mL14.8205mL29.6410mL5mM0.5928mL2.9641mL5.9282mL10mM0.2964mL1.4821mL2.9641mL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(storedundernitrogen)。-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：1%DMSO>>99%salineSolubility:0.5mg/mL(1.48mM);Suspendedsolution;Needultrasonic1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(6.17mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.17mM);Clearsolution4.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.17mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(7.41mM);Clearsolution6.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(7.41mM);ClearsolutionBIOLOGICALACTIVITY?物活性Voxelotor(GBT440)?種有效的鐮狀?紅蛋?(HbS)聚合抑制劑。Voxelotor有潛??于鐮狀細(xì)胞貧?病的研究[1]。IC50&TargetHbSpolymerization[1]體外研究Voxelotor(GBT440)bindstotheN-terminalachainofhaemoglobin(Hb),increaseshaemoglobinS(HbS)affinityforoxygen,delaysinvitroHbSpolymerizationandpreventssicklingofredbloodcells(RBCs)[1].體內(nèi)研究Voxelotor(GBT440;100-150mg/kg;administeredtwiceadaybyoralgavagefor9-12days)reducesexvivosicklingandprolongsredbloodcells(RBCs)half-lifeinamurinemodelofsicklecelldisease(SCD)[1].VoxelotorshowsT1/2sof11.7,19.1±1.5,66.0±11,28.8±4.0hoursformouse(70mg/kg;i.v.),rat(1.6mg/kg;i.v.),dog(1mg/kg;i.v.),andmomkey(1mg/kg;i.v.),respectively[1].VoxelotorshowsCmaxsof81.9,71.2±6.0,5.56±1.6,and25.2±5.5μg/mLformouse(30mg/kg;p.o.),rat(7.2mg/kg;p.o.),dog(2.5mg/kg;p.o.),andmomkey(4.25mg/kg;p.o.),respectively[1].AnimalModel:HbSSTownesknock-insicklemice(SSmice)[1]Dosage:100and150mg/kgAdministration:Oraladministration;twiceaday;for9-12daysResult:Reducedhaemolysis.AnimalModel:C57BL/6Jmice,Sprague-Dawleyrats,BeagledogsandCynomolgusmonkeys[1]Dosage:70,1.6,1and1mg/kgformice,rats,dogsandmonkeys,respectively30,7.2,2.5and4.25mg/kgformice,rats,dogsandmonkeys,respectivelyAdministration:Intravenous(IV:70,16,1and1mg/kg,respectively)Oral(PO:30,72,25and43mg/kg,respectively)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEResult:T1/2sof11.7,19.1±1.5,66.0±11,28.8±4.0hoursformouse(70mg/kg;i.v.),rat(1.6mg/kg;i.v.),dog(1mg/kg;i.v.),andmomkey(1mg/kg;i.v.),respectively.Cmaxsof81.9,71.2±6.0,5.56±1.6,and25.2±5.5μg/mLformouse(30mg/kg;p.o.),rat(7.2mg/kg;p.o.),dog(2.5mg/kg;p.o.),andmomkey(4.25mg/kg;p.o.),respectively.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?AmJHematol.2019May;94(5):575-584.?Pharmaceutics.2021,13(9),1388.?SciRep.2020Nov20;10(1):20277.?JPharmBiomedAnal.2022:115152.?AmJClinPathol.2020Oct13;154(5):627-634.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].OksenbergD,etal.GBT440increaseshaemoglobinoxygenaffinity,reducessicklingandprolongsRBChalf-lifeinamurinemodelofsicklecelldisease.BrJHaematol.2016Oct;175(1):141-53.McePdfHeightCauti