Abstract
The patent presents 140 purine and 7-azapurine derivatives as potent inhibitors of DOT1L histone methyltransferase that might be useful in the treatment of leukemia with MLL rearrangements. It is becoming more and more evident that the deregulation of chromatin modifiers such as DOT1L plays a critical role in tumorigenesis. As yet, the number of pharmaceutical agents targeting chromatin modifiers is still limited. The market for such compounds has been estimated to be potentially as large as one third of all cancer patients. Overall, the prospective of a targeted product (i.e., a drug targeting a commonly affected chromatin modifier) is very promising, and exponentially growing investments into this market are anticipated.
MeSH terms
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Drug and Narcotic Control
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Epigenesis, Genetic / drug effects*
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Gene Expression Regulation, Neoplastic / drug effects
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Histone-Lysine N-Methyltransferase
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Humans
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Leukemia / drug therapy*
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Leukemia / enzymology
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Leukemia / genetics
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Leukemia / pathology
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Methyltransferases / antagonists & inhibitors*
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Methyltransferases / metabolism
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Molecular Structure
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Molecular Targeted Therapy*
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Patents as Topic
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Purines / chemistry
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Purines / pharmacology*
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Purines / therapeutic use
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Structure-Activity Relationship
Substances
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7-deazapurine
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Antineoplastic Agents
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Enzyme Inhibitors
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Purines
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DOT1L protein, human
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Methyltransferases
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Histone-Lysine N-Methyltransferase