Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemE1A-116Cat.No.:HY-104064CASNo.:1430208-73-3分?式:C??H??F?N?分?量:307.31作?靶點(diǎn):Ras;Apoptosis作?通路:GPCR/GProtein;Apoptosis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:100mg/mL(325.40mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM3.2540mL16.2702mL32.5404mL5mM0.6508mL3.2540mL6.5081mL10mM0.3254mL1.6270mL3.2540mL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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)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%salineSolubility:≥2.5mg/mL(8.14mM);Clearsolution1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(8.14mM);Suspendedsolution;Needultrasonic3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(8.14mM);ClearsolutionBIOLOGICALACTIVITY?物活性1A-116?種對(duì)W56殘具有特異性的Rac1抑制劑，能有效防?EGF誘導(dǎo)的Rac1激活，并阻斷Rac1-P-Rex1的相互作?。1A-116能以晝夜節(jié)律依賴的?式誘導(dǎo)細(xì)胞凋亡并抑制細(xì)胞的增殖、遷移和周期進(jìn)展。1A-116在體內(nèi)也具有較?的抗癌細(xì)胞轉(zhuǎn)移活性。IC50&TargetIC50:4μM(F3II);21μM(MDA-MB-231)[1].Rac1[1]Apoptosis[2]體外研究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?邊的抑制劑?師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.體內(nèi)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?邊的抑制劑?師www.MedChemEAnimalModel:MaleNIHSwissfoxN1(?/?)nudemice(2-month-old;GBMmodel)[2].Dosage:20mg/kgAdministration:Intraperitonealinjection(atZT3,ZT12);onceaday,73daysforZT12,68daysforZT3.Result:IncreasedsurvivaltimewhentreatedatZT12comparedtoZT3intumor-bearingmice.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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