Parsaclisib-INCB050465-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEParsaclisibCat.No.:HY-109068CASNo.:1426698-88-5Synonyms:INCB050465分⼦式:C₂₀H₂₂ClFN₆O₂分⼦量:432.88作⽤靶点:PI3K作⽤通路:PI3K/Akt/mTOR储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:125mg/mL(288.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.3101mL11.5505mL23.1011mL5mM0.4620mL2.3101mL4.6202mL10mM0.2310mL1.1551mL2.3101mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.81mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.81mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.81mM);Clearsolution4.请依序添加每种溶剂：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.78mM);Clearsolution5.请依序添加每种溶剂：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.78mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Parsaclisib(INCB050465)⼀种有效，选择性和具有⼝服活性的PI3Kδ抑制剂，IC50值为1nM。Parsaclisib相对于其他PI3KI类同⼯型的选择性约为20000倍。Parsaclisib可⽤于研究复发或难治性B细胞恶性肿瘤。IC50&TargetPI3Kδ1nM(IC50)体外研究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.体内研究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)inPfeiffersubcutaneousmousexenograft2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEmodels[2].AnimalModel:FemaleBALB/cmice(5-9weeks)wereinoculatedwithA20cells[2]Dosage:10mg/kgAdministration:Oralgavagetwicedailyfor7-19daysResult:Resultedinsignificanttumorgrowthinhibition(TGI).ReducedthepercentageofTregs(CD4+CD25+FOXP3+)intumorsandspleens.IncreasedtheratioofCD4+andCD8+TcellstoTregsinspleensandtumors.DecreasedthenumberofCD4+CD44highandCD8+CD44highTcellsinbothspleensandtumors.REFERENCES[1].NiuShin,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.McePdfHeightCau