| Invitro | SKLB-23bbshowscytotoxiceffectsagainstapanelofsolidandhematologictumorcelllinesatthelowsubmicromolarlevel.IncontrasttothereportedHDAC6-selectiveinhibitors,SKLB-23bbismoreefficientagainstsolidtumorcells.SKLB-23bbselectivelyinhibitscellularHDAC6,buttheantitumoractivityofSKLB-23bbisindependentofHDAC6.SKLB-23bbcouldbindtothecolchicinesiteinβ-tubulinandactasamicrotubulepolymerizationinhibitor.ItblockstumorcellcycleatG2-Mphaseandtriggerscellularapoptosis[1]. |
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| Assay | | Methods | TestIndex | PMID |
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| Westernblot | Ac-α-tubulin/Ac-H3; PubMed:29610282 Westernblotanalysisofacetylatedα-tubulin,acetylatedhistoneH3inhct116,A2780s,andU266celllinesafter6hoursoftreatmentwithSKLB-23bb,ACY-1215,orSAHAattheindicatedconcentrations.GAPDHwasusedasaloADIngcontrol. p-H3; PubMed:29610282 Analysisofp-H3level.ConcentrationofSKLB-23bb,200nmol/L;ConcentrationofACY1215,10μmol/L. PARP/CF-PARP/Caspase3/CF-caspase3/Caspase9/CF-Caspase9; PubMed:29610282 EffectsofSKLB-23bbonPARP,caspase-3,andcaspase-9inhct116andA2780scellsexaminedbyWesternblotting.ConcentrationofSKLB-23bbintheanalysisofincreasingtimepoints:1,000nmol/L.Arrow,cleavedcaspase-9;asterisk,nonspecificband. 29610282 | | Immunofluorescence | α-tubulin; PubMed:29610282 EffectofSKLB-23bbandotherreferencecompoundsontheorganizationofcellularmicrotubulenetwork.TubulinareshowningreenandtheNucleiinblue.Col,colchicine;PTX,paclitaxel. 29610282 | | Growthinhibitionassay | Cellviability; PubMed:29610282 AnalysisofthecytotoxiceffectsofSKLB-23bbagainstHDAC6knockoutcelllinescomparedwiththeparentones.Left,hct116background.Right,A2780sbackground. 29610282 | | Invivo | Insolidtumorxenografts,oraladmiNISTrationofSKLB-23bbefficientlyinhibitstumorgrowth.SKLB-23bbhasgoodpharmacokineticprofilesandisorallybioavailable[1]. |
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