Abstract
A series of analogs of 3-(2-amino-ethyl)-5-(4-ethoxy-benzylidene)-thiazolidine-2,4-dione, a putative substrate-specific ERK1/2 inhibitor, were synthesized and biologically characterized in human leukemia U937 cells to define its pharmacophore. It was discovered that shift of ethoxy substitution from the 4- to the 2-position on the phenyl ring significantly improved functional activities of inhibiting cell proliferation and inducing apoptosis. This may provide access to a new lead for developing ERK1/2 substrate-specific inhibitors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Catalytic Domain
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Cell Line, Tumor
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Cell Proliferation
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Computer Simulation
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Humans
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors*
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Mitogen-Activated Protein Kinase 3 / metabolism
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Phosphorylation
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Protein Kinase Inhibitors / chemical synthesis
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Protein Kinase Inhibitors / chemistry*
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Protein Kinase Inhibitors / pharmacology
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Structure-Activity Relationship
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Substrate Specificity
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Thiazolidinediones / chemical synthesis
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Thiazolidinediones / chemistry*
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Thiazolidinediones / pharmacology
Substances
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3-(2-aminoethyl)-5-(4-ethoxybenzylidene)thiazolidine-2,4-dione
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Protein Kinase Inhibitors
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Thiazolidinediones
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Mitogen-Activated Protein Kinase 3