Abstract
The natural product-like compound 1 was identified as a direct inhibitor of the menin-MLL interaction by in silico screening. Structure-based optimization furnished analogue 1a, which showed significantly higher potency than both the lead structure 1 and the reference compound MI-2.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaloids / chemistry*
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Alkaloids / pharmacology
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Azocines / chemistry
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Azocines / pharmacology
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Hep G2 Cells
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Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
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Humans
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Models, Molecular
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Myeloid-Lymphoid Leukemia Protein / antagonists & inhibitors*
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Protein Binding
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Quinolizines / chemistry
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Quinolizines / pharmacology
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Structure-Activity Relationship
Substances
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Alkaloids
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Antineoplastic Agents
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Azocines
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KMT2A protein, human
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MEN1 protein, human
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Proto-Oncogene Proteins
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Quinolizines
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Myeloid-Lymphoid Leukemia Protein
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cytisine
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Histone-Lysine N-Methyltransferase