| Description | SKLB-610isamulti-targetinhibitorofthetyrosinekinases.ItismostpotentagainstVEGFR2andexhibitsslightlyweakerinhibitorofFGFR2andPDGFR. | |||||
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| Invitro | Invitro,SKLB610showsselectiveinhibitionofVEGF-stimulatedhumanumbilicalveinendothelialcells(HUVECs)proliferation,andthisproliferationinhibitoryeffectisassociatedwithdecreasedphosphorylationofVEGFR2andp42/44mitogen-activatedproteinkinase(p42/44MAPK).SKLB610inhibitsapanelofhumancancercellsproliferationinaconcentration-dependentmannerandhumannonsmallcelllungcancercelllineA549andhumancolorectalcancercelllineHCT116aremostsensitivetoSKLB610treatment.Atconcentrationof10μM,SKLB610inhibits65%FGFR2activityand55%PDGFREactivity,respectively.RelativetoPDGFR2andFGFR2SKLB610hasmoreselectiveinhibitionofVEGFR2whichshows97%inhibitionofVEGFR2activityat10μMinvitro.Noinhibitionofenzymeactivityisdetectedwhen10μMofSKLB610isexaminedagainstPI3K,EGFR,Aurora-A,CDK2/cyclinEandCDK6/cyclinD3[1]. | |||||
| Invivo | Invivo,chronicintraperitoneallyadmiNISTrationofSKLB610atdoseof50mg/kg/dresultsinsignificantinhibitioninthegrowthofestablishedhumanA549andHCT116tumorxenograftsinnudemicewithoutexhibittoxicity[1]. |
