Tovinontrine-IMR-687-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETovinontrineCat.No.:HY-109193CASNo.:2062661-53-2Synonyms:IMR-687分?式:C??H??N?O?分?量:394.47作?靶點(diǎn):Phosphodiesterase(PDE)作?通路:MetabolicEnzyme/Protease儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(253.50mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.5350mL12.6752mL25.3505mL5mM0.5070mL2.5350mL5.0701mL10mM0.2535mL1.2675mL2.5350mL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。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時(shí)，請?jiān)?個?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)動物和給藥?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，澄的儲備液可以根據(jù)儲存條件，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%saline1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(6.34mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.34mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.34mM);ClearsolutionBIOLOGICALACTIVITY?物活性Tovinontrine(IMR-687)?種?效的選擇性磷酸?酯酶9(PDE9)抑制劑，可?于研究鐮狀細(xì)胞病。抑制PDE9A1和PDE9A2的IC50分別為8.19nM和9.99nM[1]。IC50&TargetPDE9A1PDE9A2PDE1A3PDE1B8.19nM9.99nM88.4nM8.48nMPDE1CPDE5A212.2nM81.9nM體外研究IMR-687inhibitsPDE9Awithmorethan800-foldgreaterpotencythanPDE1A3,PDE1B,PDE1C,PDE5A2,withIC50valuesof88.4μM,8.48μM,12.2μM,and81.9μM,respectively[1].IMR-687(0.1-10μM)treatmentinerythroidK562cellsfor72hoursinduceshemoglobin(HbF)inadose-dependentmanner[1].IMR-687(0.03-10μM)treatmentfor6hoursinerythroidK562cellsincreasescGMPinadose-dependentmanner[1].體內(nèi)研究IMR-687(30mg/kg/day;after30daysoftreatment)showsagreaterthan3-foldinthepercentofHbF+F-cells(8.4%invehicletreatedand27.3%inIMR-687treated)andacorresponding2-folddecreaseinsickledredbloodcells(56.3%invehicletreatedand24.4%inIMR-687treated)[1].AnimalModel:HbSS-Townesmiceona129/B6background(10-12weeksold)[1]Dosage:30mg/kgAdministration:Doseddailybygavagefor30daysResult:Resultedinfetalhemoglobin(HbF)induction,reducedhemolysisandreducedreticulocytosis.REFERENCES[1].JamesGMcArthur,etal.Anovel,highlypotentandselectivephosphodiesterase-9inhibitorforthetreatmentofsicklecelldisease.Haematologica.2020Mar;105(3):623-631.McePdfHeight2/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemECaution:Producthasnotbeenfullyvalidatedformedicalapplicati