Abstract
Pyrrolo[3,4-c]carbazoles bearing solubilising basic side chains at the 8-position retain potent Wee1 and Chk1 inhibitory properties in isolated enzyme assays, and evidence of G2/M checkpoint abrogation in several cellular assays. Co-crystal structure studies confirm that the primary binding to the Wee1 enzyme is as described previously, with the C-8 side chains residing in an area of bulk tolerance.
MeSH terms
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Carbazoles / chemical synthesis*
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Carbazoles / chemistry
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Carbazoles / pharmacology*
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Cell Cycle Proteins / antagonists & inhibitors*
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Checkpoint Kinase 1
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Combinatorial Chemistry Techniques*
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Humans
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Molecular Structure
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Nuclear Proteins / antagonists & inhibitors*
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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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Protein Kinases / metabolism*
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Structure-Activity Relationship
Substances
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Carbazoles
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Cell Cycle Proteins
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Nuclear Proteins
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Protein Kinase Inhibitors
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Protein Kinases
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Protein-Tyrosine Kinases
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WEE1 protein, human
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CHEK1 protein, human
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Checkpoint Kinase 1