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Selleckchem/SKLB-23bb/S8743

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S8743

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Selleck Chemicals

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DescriptionSKLB-23bbisanorallybioavailableHDAC6-selectiveinhibitorwithIC50valuesunder100nmol/L,againstmostofthecelllineschecked.Italsohasmicrotubule-disruptingABIlity.TargetsHDAC6[1](Cell-basedassay)InvitroSKLB-23bbshowscytotoxiceffectsagainstapanelofsolidandhematologictumorcelllinesatthelowsubmicromolarlevel.IncontrasttothereportedHDAC6-selectiveinhibitors,SKLB-23bbismoreefficientagainstsolidtumorcells.SKLB-23bbselectivelyinhibitscellularHDAC6,buttheantitumoractivityofSKLB-23bbisindependentofHDAC6.SKLB-23bbcouldbindtothecolchicinesiteinβ-tubulinandactasamicrotubulepolymerizationinhibitor.ItblockstumorcellcycleatG2-Mphaseandtriggerscellularapoptosis[1].AssayMethodsTestIndexPMIDWesternblotAc-α-tubulin/Ac-H3;PubMed:29610282MolCancerTherWesternblotanalysisofacetylatedα-tubulin,acetylatedhistoneH3inhct116,A2780s,andU266celllinesafter6hoursoftreatmentwithSKLB-23bb,ACY-1215,orSAHAattheindicatedconcentrations.GAPDHwasusedasaloADIngcontrol.p-H3;PubMed:29610282MolCancerTherAnalysisofp-H3level.ConcentrationofSKLB-23bb,200nmol/L;ConcentrationofACY1215,10μmol/L.PARP/CF-PARP/Caspase3/CF-caspase3/Caspase9/CF-Caspase9;PubMed:29610282MolCancerTherEffectsofSKLB-23bbonPARP,caspase-3,andcaspase-9inhct116andA2780scellsexaminedbyWesternblotting.ConcentrationofSKLB-23bbintheanalysisofincreasingtimepoints:1,000nmol/L.Arrow,cleavedcaspase-9;asterisk,nonspecificband.29610282Immunofluorescenceα-tubulin;PubMed:29610282MolCancerTherEffectofSKLB-23bbandotherreferencecompoundsontheorganizationofcellularmicrotubulenetwork.TubulinareshowningreenandtheNucleiinblue.Col,colchicine;PTX,paclitaxel.29610282GrowthinhibitionassayCellviability;PubMed:29610282MolCancerTherAnalysisofthecytotoxiceffectsofSKLB-23bbagainstHDAC6knockoutcelllinescomparedwiththeparentones.Left,hct116background.Right,A2780sbackground.29610282InvivoInsolidtumorxenografts,oraladmiNISTrationofSKLB-23bbefficientlyinhibitstumorgrowth.SKLB-23bbhasgoodpharmacokineticprofilesandisorallybioavailable[1].

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