
Description | ZT-12-037-01isaspecificandATP-competitiveSTK19inhibitorwithIC50sof23.96nMand27.94nMforSTK19(WT)andSTK19(D89N),respectively.ItdisplaysextremelyhighkinaseselectivityusingKINOMEscanagainstapanelof468diversekinasesusinganinvitroATP-sitecompetitionbindingassayat1μM. | ||||
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Targets |
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Invitro | ZT-12-037-01treatmentefficientlyinhibitsphosphorylationofNRASinadose-andtime-dependentmanner.FurThermore,withincreasingATPconcentrations,theIC50ofZT-12-037-01againstSTK19accordinglyincreased,indicatingthatZT-12-037-01isanATP-competitiveinhibitorforSTK19.ZT-12-037-01treatmentsignificantlyinhibitsmutantNRAS-STK19-drivenmelanocytecolonyformation,proliferation,andtumorformation.Pro-apoptoticeffectofZT-12-037-01isdramaticallyenhancedincellsexpressingoncogenicNRAS[1]. | ||||
Invivo | ZT-12-037-01isahighlypotentSTK19inhibitorwithlowinvivotoxicity.ItstreatmentalsoinhibitsgrowthofSK-MEL-2xenograftmelanoma(withNRASQ61R)inadose-dependentmanner[1]. |
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