Parsaclisib-INCB050465-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEParsaclisibCat.No.:HY-109068CASNo.:1426698-88-5Synonyms:INCB050465分?式:C??H??ClFN?O?分?量:432.88作?靶點(diǎn):PI3K作?通路:PI3K/Akt/mTOR儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:125mg/mL(288.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3101mL11.5505mL23.1011mL5mM0.4620mL2.3101mL4.6202mL10mM0.2310mL1.1551mL2.3101mL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。-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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.81mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.81mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.81mM);Clearsolution4.請(qǐng)依序添加每種溶劑：5%DMSO>>40%PEG300>>5%Tween-80>>50%salineSolubility:≥2.5mg/mL(5.78mM);Clearsolution5.請(qǐng)依序添加每種溶劑：5%DMSO>>95%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.78mM);ClearsolutionBIOLOGICALACTIVITY?物活性Parsaclisib(INCB050465)?種有效，選擇性和具有?服活性的PI3Kδ抑制劑，IC50值為1nM。Parsaclisib相對(duì)于其他PI3KI類同?型的選擇性約為20000倍。Parsaclisib可?于研究復(fù)發(fā)或難治性B細(xì)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(nèi)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?邊的抑制劑?師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