Abstract
Anaplastic lymphoma kinase (ALK) receptor tyrosine kinase is considered a promising therapeutic target for human cancers. We identified novel tetracyclic derivatives as potent ALK inhibitors. Among them, compound 27 showed strong cytotoxicity against KARPAS-299 with an IC(50) value of 21 nM and significant antitumor efficacy in ALK fusion-positive blood and solid cancer xenograft models in mice without body weight loss.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Anaplastic Lymphoma Kinase
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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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Disease Models, Animal
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Drug Discovery*
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Enzyme Activation / drug effects
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Humans
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Inhibitory Concentration 50
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Mice
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Molecular Structure
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Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
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Tetracyclines / chemical synthesis*
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Tetracyclines / chemistry
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Tetracyclines / pharmacology
Substances
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Antineoplastic Agents
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Tetracyclines
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ALK protein, human
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Alk protein, mouse
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Anaplastic Lymphoma Kinase
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Receptor Protein-Tyrosine Kinases