CGI-1746-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECGI-1746Cat.No.:HY-11999CASNo.:910232-84-7分⼦式:C₃₄H₃₇N₅O₄分⼦量:579.69作⽤靶点:Btk;Autophagy作⽤通路:ProteinTyrosineKinase/RTK;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥50mg/mL(86.25mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM1.7251mL8.6253mL17.2506mL5mM0.3450mL1.7251mL3.4501mL10mM0.1725mL0.8625mL1.7251mL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:≥2.5mg/mL(4.31mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(4.31mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.31mM);SuspendedsolutionBIOLOGICALACTIVITY⽣物活性CGI-1746⼀种有效的，⾼选择性的Btk抑制剂，IC50值为1.9nM。IC50&TargetIC50:1.9nM(Btk)体外研究CGI1746isspecificforBtk,withappr1,000-foldselectivityoverTecandSrcfamilykinases.InanATP-freecompetitionbindingassay,thedissociationconstantforBtkis1.5nM.CGI1746inhibitsBtkactivityinanewbindingmodethatstabilizesaninactivenonphosphorylatedenzymeconformation.CGI1746inhibitsbothauto-andtransphosphorylationstepsnecessaryforenzymeactivation.CGI1746completelyinhibitsanti-IgM-inducedmurineandhumanBcellproliferation,withIC50sof134nMand42nM,respectively,buthasnoeffectonanti-CD3-andanti-CD28-inducedTcellproliferation.CGI1746potentlyinhibitstheproliferationofCD27+IgG+BcellsisolatedfromthetonsilsoffourhumandonorswithanaverageIC50of112nM.Inmacrophages,CGI1746abolishesFcγRIII-inducedTNFα,IL-1βandIL-6production.CGI1746potentlyinhibitsTNFα,IL-1βand,toalesserextent,IL-6(three-toeight-foldhigherIC50)productioninhumanmonocytesstimulatedwithimmobilizedorsolubleimmunecomplexes[1].CGI-1746doesnotkillcellsaswellastheirreversibleBTKinhibitorsatthesamedrugconcentration.CGI-1746significantlyreducesphosphorylationofboththeBTK-AandBTK-Cproteins,indicatingtheauto-phosphorylationoftheBTK-CisoformisinhibitedinamannersimilartoBTK-A.CGI-1746doesnotkillLNCaPorDU145prostatecancercellsatthesameconcentrationsasIbrutiniborAVL-292,butitdemonstratessimilarinhibitionofBTKphosphorylationattyrosine233intheSH3domain[2].体内研究CGI1746abrogatesBcell-dependentarthritis.CGI1746treatment(100mg/kg,s.c,twice-dailydosing)resultsinsignificantinhibition(97%)ofoverallclinicalarthritisscores.CGI1746treatmentsubstantiallyreducesTNFα,IL-1βandIL-6,aswellasMCP1andMIP-1αonboththemRNAandproteinlevelinthepassiveanti-collagenIIantibody-inducedarthritis(CAIA)model.CGI1746showscomparableefficacytoTNFαblockadeandsignificantlyreducesclinicalscores,aswellasjointinflammation,inmiceorratswithestablishedarthritis[1].PROTOCOLCellAssay[2]5×103DU145cellsor104LNCaPcellsperwell,grownon96wellplatesfor24h,aretreatedwith1to30µMBTKinhibitors.Cellsarefixedafter72hwith2.5%formaldehyde,andstainedwithHoechst33342.ControlcellsaretreatedwithDMSO.CellimagesareacquiredusinganINCellAnalyzer2200highcontentimagingsystem,witha20Xobjective.Atleast9fieldsareimagedpersinglewellofeachexperiment.CellnumbersaredeterminedandstatisticsperformedusingINCellInvestigator3.4highcontentimageanalysissoftware.2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEEachexperimentisreplicated3times,anddataarepresentedasmean±SD.Resultsareconsideredsignificantifp<0.05.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Leukemia.2021Feb1.•MolPharmacol.2017Mar;91(3):208-219.•JBiomolScreen.2015Aug;20(7):876-86.•Patent.US20190040013A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DiPaolo,JulieA.etal.SpecificBtkinhibitionsuppressesBcell-andmyeloidcell-mediatedarthritis.NatureChemicalBiology(2011),7(1),41-50[2].KokabeeL,etal.Bruton'styrosinekinaseisapotentialtherapeutictargetinprostatecancer.CancerBiol