1A-116-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemE1A-116Cat.No.:HY-104064CASNo.:1430208-73-3分⼦式:C₁₆H₁₆F₃N₃分⼦量:307.31作⽤靶点:Ras;Apoptosis作⽤通路:GPCR/GProtein;Apoptosis储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(325.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM3.2540mL16.2702mL32.5404mL5mM0.6508mL3.2540mL6.5081mL10mM0.3254mL1.6270mL3.2540mL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%salineSolubility:≥2.5mg/mL(8.14mM);Clearsolution1/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(8.14mM);Suspendedsolution;Needultrasonic3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.14mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性1A-116⼀种对W56残具有特异性的Rac1抑制剂，能有效防⽌EGF诱导的Rac1激活，并阻断Rac1-P-Rex1的相互作⽤。1A-116能以昼夜节律依赖的⽅式诱导细胞凋亡并抑制细胞的增殖、迁移和周期进展。1A-116在体内也具有较⾼的抗癌细胞转移活性。IC50&TargetIC50:4µM(F3II);21µM(MDA-MB-231)[1].Rac1[1]Apoptosis[2]体外研究1A-116(48h)inhibitsF3IIandMDA-MB-231cellsproliferationinaconcentration-dependentmannerwithIC50sof4µMand21µM,respectively[1].1A-116(1,10µM;12h)dramaticallyimpairesRac1activation,andreducesRac1-GTPintracellularlevelsinaconcentration-dependentmannerinF3IIcells[1].1A-116(50,100µM;12h)blocksRac1-P-Rex1interaction[1].1A-116(20µM;5hintervalsover25h)inhibitsLN229cellsproliferationinacircadianmanner[2].1A-116(10µM;16h)significantlyreducescellmigrationat10HPSwhichexhibitstemporaldependence.(HPS:Aftertheserumshock,theelapsedtime(inhours)isrecordedasthehourspost-synchronization(HPS))[2].1A-116(20,50µM;6h)inducescellsapoptosisandinacircadian-dependentmanner[2].1A-116(100nM)decreasesthethicknessoftheepidermallayersofVav2andRac1-mediatedhyperplasia,butnotthePAK1-mediatedone,whichexhibitstheactivityofinhibitingRac1attheGEF-Rac1level[3].CellProliferationAssay[1][2]CellLine:MDA-MB-231,F3II,LN229cellsConcentration:20µMIncubationTime:48h;5hintervalsover25h.Result:Inhibitedcellproliferationinaconcentration-dependentandcircadianmanner.CellViabilityAssay[3]CellLine:Ker-CThumankeratinocytescellswithoncogenicVav2/Rac1F28L/PAK1Tyrosine423Concentration:100nMIncubationTime:2/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEResult:InhibitedRac1activityattheGEF-Rac1level.CellMigrationAssay[2]CellLine:LN229cellsConcentration:10µMIncubationTime:16hResult:Reducedcellmigrationat10HPSwhichexhibitedtemporaldependence.ApoptosisAnalysis[2]CellLine:LN229cellsConcentration:20,50µMIncubationTime:6hResult:Inducedcellsapoptosisandinacircadian-dependentmanner.WesternBlotAnalysis[1]CellLine:F3IIcellsConcentration:1,10µMIncubationTime:12hResult:BlockedRac1-P-Rex1interaction.ReducedRac1-GTPintracellularlevelsinaconcentration-dependentmanner.体内研究1A-116(3mg/kg;i.v.;onceadayfor21days)demonstratesahighantimetastaticactivitywithabout60%formationreductionoftotalmetastaticlungcoloniesinvivoandshowsnoapparenttoxicity[1].1A-116(20mg/kg;i.p.;onceaday,73daysforZT12,68daysforZT3)increasessurvivaltimewhentreatedatZT12comparetoZT3intumor-bearingmice.(ZT:Zeitgebertime12(ZT12)definedasthetimeoflightsoff(localtime7p.m.)andZT0definedaslightson(localtime7a.m.))[2].1A-116showsgoodoralavailability[3].AnimalModel:FemaleBALB/cinbredmice(8to10-week-old;average20g)[1]Dosage:3mg/kgAdministration:Intravenousinjection;onceadayfor21days.Result:Demonstratedahighantimetastaticactivity.3/4MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAnimalModel:MaleNIHSwissfoxN1(∆/∆)nudemice(2-month-old;GBMmodel)[2].Dosage:20mg/kgAdministration:Intraperitonealinjection(atZT3,ZT12);onceaday,73daysforZT12,68daysforZT3.Result:IncreasedsurvivaltimewhentreatedatZT12comparedtoZT3intumor-bearingmice.户使⽤本产品发表的科研⽂献•CurrBiol.2021Jul27;S0960-9822(21)00959-3.•ClinTranslMed.2022Jun;12(6):e850.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].TrebucqLL,etal.TimingofNovelDrug1A-116toCircadianRhythmsImprovesTherapeuticEffectsagainstGlioblastoma.Pharmaceutics.2021Jul16;13(7):1091.[2].GonzálezN,etal.ComputationalandinvitroPharmacodynamicsCharacterizationof1A-116Rac1Inhibitor:RelevanceofTrp56inItsBiologicalActivity.FrontCellDevBiol.2020Apr15;8:240.[3].CardamaGA,etal.PreclinicaldevelopmentofnovelRac1-GEFsignalinginhibitorsusingarationaldesignapproachinhighlyaggressivebreastcancercelll