Abstract
Novel substituted pteridine-derived inhibitors of monocarboxylate transporter 1 (MCT1), an emerging target for cancer therapy, are reported. The activity of these compounds as inhibitors of lactate transport was confirmed using a (14)C-lactate transport assay, and their potency against MCT1-expressing human tumor cells was established using MTT assays. The four most potent compounds showed substantial anticancer activity (EC50 37-150 nM) vs MCT1-expressing human Raji lymphoma cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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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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Biological Transport / drug effects
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Cell Line, Tumor
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Humans
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Lactic Acid / metabolism
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MCF-7 Cells
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Mice
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Models, Chemical
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Molecular Structure
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Monocarboxylic Acid Transporters / antagonists & inhibitors*
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Monocarboxylic Acid Transporters / metabolism
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Pteridines / chemical synthesis
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Pteridines / chemistry
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Pteridines / pharmacology*
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Structure-Activity Relationship
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Symporters / antagonists & inhibitors*
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Symporters / metabolism
Substances
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Antineoplastic Agents
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Monocarboxylic Acid Transporters
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Pteridines
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Symporters
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monocarboxylate transport protein 1
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Lactic Acid