Parsaclisib-hydrochloride-INCB050465-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEParsaclisibhydrochlorideCat.No.:HY-109068ACASNo.:1995889-48-9Synonyms:INCB050465hydrochloride分?式:C??H??Cl?FN?O?分?量:469.34作?靶點:PI3K作?通路:PI3K/Akt/mTOR儲存?式:4°C,storedundernitrogen*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen)溶解性數(shù)據(jù)體外實驗DMSO:240mg/mL(511.36mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.1307mL10.6533mL21.3065mL5mM0.4261mL2.1307mL4.2613mL10mM0.2131mL1.0653mL2.1307mL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(storedundernitrogen)。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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:≥6mg/mL(12.78mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥6mg/mL(12.78mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥6mg/mL(12.78mM);ClearsolutionBIOLOGICALACTIVITY?物活性Parsaclisibhydrochloride(INCB050465hydrochloride)?種有效，選擇性和具有?服活性的PI3Kδ抑制劑，IC50值為1nM。Parsaclisibhydrochloride相對于其他PI3KI類同?型的選擇性約為20000倍。Parsaclisibhydrochloride可?于研究復發(fā)或難治性B細胞惡性腫瘤。IC50&TargetPI3Kδ1nM(IC50)體外研究Parsaclisib(0.1-3000nM;4d)inhibitsproliferationofMCLandDLBCLcelllines[2].Parsaclisib(0.1-1000nM;2h)inhibitsanti-IgM-inducedpAKT(Ser473)intheRamosBurkitt’slymphomacellline,withanIC50of1nM[2].Parsaclisibinhibitstheproliferationofhuman,dog,rat,andmouseprimaryBcellsafteractivationofthesereceptors,withIC50srangingfrom0.2to1.7nM[2].CellProliferationAssay[2]CellLine:Jeko-1,Mino,JVM2,Rec-1,Pfeiffer,SU-DHL-5,SU-DHL-6,WSU-NHL,SU-DHL-4,SU-DHL-8,andWILL-2cellsConcentration:0.1-3000nMIncubationTime:4daysResult:Resultedinamaximalinhibitionof70-90%,withIC50sof≤10nMinthefourMCLcelllines.Pfeiffer,SU-DHL-5,SU-DHL-6,andWSU-NHLwerehighlysensitive,withIC50sfrom2to8nM.體內研究Parsaclisib(10mg/kg;oralgavagetwicedailyfor7-19days)inhibitstumorgrowthintheBALB/cmicebearingtheA20murinelymphomacells[2].Parsaclisib(0.1-10mg/kg;p.o.twicedaily)slowsPfeifferxenografttumorgrowthinadose-dependentmanner.AndParsaclisibwaswelltolerated[2].Parsaclisib(0.5-1mg/kg;asinglep.o.)inhibitspAKT(Ser473)inPfeiffersubcutaneousmousexenograftmodels[2].AnimalModel:FemaleBALB/cmice(5-9weeks)wereinoculatedwithA20cells[2]Dosage:10mg/kg2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEAdministration:Oralgavagetwicedailyfor7-19daysResult:Resultedinsignificanttumorgrowthinhibition(TGI).ReducedthepercentageofTregs(CD4+CD25+FOXP3+)intumorsandspleens.IncreasedtheratioofCD4+andCD8+TcellstoTregsinspleensandtumors.DecreasedthenumberofCD4+CD44highandCD8+CD44highTcellsinbothspleensandtumors.REFERENCES[1].ShinN,etal.Abstract2671:INCB050465,anovelPI3Kδinhibitor,synergizeswithPIMproteinkinaseinhibitiontocausetumorregressioninamodelofDLBCL.CancerResearch.2015,Aug.75(15).[2].ShinN,et,al.ParsaclisibIsaNext-GenerationPhosphoinositide3-KinaseδInhibitorwithReducedHepatotoxicityandPotentAntitumorandImmunomodulatoryActivitiesinModelsofB-CellMalignancy.JPharmacolExpTher.2020Jul;374(1):211-222.[3].YueEW,et,al.INCB050465(Parsaclisib),aNovelNext-GenerationInhibitorofPhosphoinositide3-KinaseDelta(PI3Kδ).ACSMedChemLett.2019Oct17;10(11):1554-1560.McePdfHeightCaution