SKI-178-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrariesSKI-178Cat.No.:HY-12892CASNo.:1259484-97-3分⼦式:C₂₁H₂₂N₄O₄分⼦量:394.42作⽤靶点:SPHK;Apoptosis作⽤通路:Immunology/Inflammation;Apoptosis储存⽅式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.溶解性数据体外实验DMSO:50mg/mL(126.77mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5354mL12.6768mL25.3537mL5mM0.5071mL2.5354mL5.0707mL10mM0.2535mL1.2677mL2.5354mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:2.5mg/mL(6.34mM);Suspendedsolution;Needultrasonic此⽅案可获得2.5mg/mL(6.34mM)的均匀悬浊液，悬浊液可⽤于⼝服和腹腔注射。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述2.体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(6.34mM);Clearsolution1/3此⽅案可获得≥2.5mg/mL(6.34mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性SKI-178⼀种有效的鞘氨醇激酶-1(SphK1)和SphK2抑制剂。SKI-178对药物敏感和多药耐药癌细胞系(如MTR3、NCI-ADR和HL60/VCR)的IC50浓度范为1.8到0.1μM。SKI-178以CDK1依赖性⽅式诱导⼈急性髓性⽩⾎病细胞凋亡。体外研究SKI-178(5μM;24hours)-inducedapoptoticcelldeathcorrelateswithprolongedBcl-2phosphorylation[1].ApoptosisAnalysis[1]CellLine:HL-60cellsConcentration:5μMIncubationTime:24hoursResult:JNKactivity(indicatedbyphosphorylationatThr183/Tyr185)increasedinatime-dependentmannerstartingasearlyas2hourscontinuedtoincreaseforatleast24hours.Therewasaconcomitantincreaseinapoptoticcelldeathindicatedbythecleavageofcaspase-7.Bcl-2phosphorylationatSer70increasedwithtimeinresponsetoSKI-178treatment,reachingmaximallevelsat8hours,whichwasconsistentwiththetimingofcaspase-7activation.体内研究SKI-178(20mg/kg;retro-orbitalinjectionunderisofluraneanesthesia)inhibitsleukemicprogressionintheMLL-AF9model[3].AnimalModel:MLL-AF9mousemodel(leukemicmice)[3]Dosage:20mg/kgAdministration:Retro-orbitalinjectionunderisofluraneanesthesia;threetimesperweekfor1and3weeksResult:Whitebloodcell(WBC)countsdecreasedfromtheirinitial104cells/μLlevelsandcontinuedtodeclineafter3weeksoftreatmentuntiltheyreachednormallevels(~4×103cells/μL).REFERENCES[1].HengstJA,etal.SKI-178:AMultitargetedInhibitorofSphingosineKinaseandMicrotubuleDynamicsDemonstratingTherapeuticEfficacyinAcuteMyeloidLeukemiaModels.CancerTranslMed.2017;3(4):109-121.2/3[2].HengstJA,etal.Developmentofasphingosinekinase1specificsmall-moleculeinhibitor.BioorgMedChemLett.2010;20(24):7498-7502.[3].DickTE,etal.Theapoptoticmechanismofactionofthesphingosinekinase1selectiveinhibitorSKI-178inhumanacutemyeloidleukemiacelllines.JPharmacolExpTher.2015;352(3):494-508.McePdf