Abstract
Structure-based drug design using the crystal structure of human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) led to the discovery of novel, selective, and the most potent inhibitors of 17beta-HSD1 reported to date. Compounds 1 and 2 contain a side chain with an m-pyridylmethyl-amide functionality extended from the 16beta position of a steroid scaffold. A mode of binding is proposed for these inhibitors, and 2 is a steroid-based 17beta-HSD1 inhibitor with the potential for further development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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17-Hydroxysteroid Dehydrogenases / antagonists & inhibitors*
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Cell Line, Tumor
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Crystallography, X-Ray
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Estrone / analogs & derivatives*
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Estrone / chemical synthesis*
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Estrone / chemistry
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Estrone / physiology
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Humans
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Models, Molecular
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Molecular Structure
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Pyridines
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Estrone
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17-Hydroxysteroid Dehydrogenases
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3 (or 17)-beta-hydroxysteroid dehydrogenase