SKI-178-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrariesSKI-178Cat.No.:HY-12892CASNo.:1259484-97-3分?式:C??H??N?O?分?量:394.42作?靶點(diǎn):SPHK;Apoptosis作?通路:Immunology/Inflammation;Apoptosis儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:50mg/mL(126.77mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5354mL12.6768mL25.3537mL5mM0.5071mL2.5354mL5.0707mL10mM0.2535mL1.2677mL2.5354mL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，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:2.5mg/mL(6.34mM);Suspendedsolution;Needultrasonic此?案可獲得2.5mg/mL(6.34mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述2.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(6.34mM);Clearsolution1/3此?案可獲得≥2.5mg/mL(6.34mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性SKI-178?種有效的鞘氨醇激酶-1(SphK1)和SphK2抑制劑。SKI-178對(duì)藥物敏感和多藥耐藥癌細(xì)胞系(如MTR3、NCI-ADR和HL60/VCR)的IC50濃度范為1.8到0.1μM。SKI-178以CDK1依賴性?式誘導(dǎo)?急性髓性??病細(xì)胞凋亡。體外研究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.體內(nèi)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