CPI-1612-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemECPI-1612Cat.No.:HY-136285CASNo.:2374971-81-8分?式:C??H??N?O分?量:450.53作?靶點:HistoneAcetyltransferase作?通路:Epigenetics儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:100mg/mL(221.96mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2196mL11.0980mL22.1961mL5mM0.4439mL2.2196mL4.4392mL10mM0.2220mL1.1098mL2.2196mL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，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?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：(為保證實驗結(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)實驗的?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%salineSolubility:5mg/mL(11.10mM);Suspendedsolution;Needultrasonic1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5mg/mL(11.10mM);ClearsolutionBIOLOGICALACTIVITY?物活性CPI-1612?種?效的具有?服活性的EP300/CBP組蛋??酰轉(zhuǎn)移酶(HAT)抑制劑，對于EP300HAT的IC50值為8.1nM。CPI-1612具有抗癌活性。IC50&TargetIC50:8.1nM(EP300HAT)[1]體外研究CPI-1612inhibitsfulllengthEP300andfulllengthCBPwithIC50values[1].CPI-1612inhibitsH3K18AcMSD(H3K18=histone3lysine18,MSD=mesoscalediscovery)andJEKO-1cellproliferationwithwithIC50values14nMand[1].CPI-1612(compound17)showsweakactivityinahERGbindingassay(IC50=10.4μM)anddisplayedmoderateinhibitionofCYP2C8(IC50=1.9μM)andCYP2C19(IC50=2.7μM)[1].體內(nèi)研究CPI-1612(compound17;0.5mg/kg;oraladministration;twiceaday;for4weeks)treatmentshows67%tumorgrowthinhibition(TGI)withconcomitantreductionofH3K27AcinplasmaandreductionofH3K18Acinthetumor[1].WhiletheoralexposureofCPI-1612(compound17)indogs(0.5mg/kgIV;1.0mg/kgPO;clearance=0.42L/h/kg,Vss=3.7L/kg,T1/2=5.5h,F%=71;AUC/dose=1691h·mg/mL)andmice(1mg/kgIV;5mg/kgPO;clearance=3.8L/h/kg,Vss=2.0L/kg,T1/2=0.98h,F%=79;AUC/dose=211h·mg/mL)isgood,theexposureinratsislimitedbypoorbioavailability(1.0mg/kgIV;5.0mg/kgPO;clearance=2.6L/h/kg,Vss=1.8L/kg,T1/2=1.2h,F%=9;AUC/dose=35.6h·mg/mL)[1].AsingledoseofCPI-1612isadministeredorallytoCD-1miceandbrainandplasmaexposuresofCPI-1612aremeasuredat0.25,0.5,1.0,2.0,4.0,and8.0h.CPI-1612ishighlybrain-penetrant,showingabrain-to-plasmaratioof0.35afterasingleoraldose[1].AnimalModel:C57B6miceinjectedwithJEKO-1cells[1]Dosage:0.5mg/kgAdministration:Oraladministration;twiceaday;for4weeksResult:Showed67%tumorgrowthinhibition(TGI)atadoseof0.5mg/kg.REFERENCES[1].JonathanEWilson,etal.DiscoveryofCPI-1612:APotent,Selective,andOrallyBioavailableEP300/CBPHistoneAcetyltransferaseInhibitor.ACSMedChemLett.2020Apr23;11(6):1324-1329.McePdfHeightCaution:Producthasnotbeenfullyvalidatedf