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Hypomethylating agent

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DNA methylation is the modification of DNA nucleotides by addition of a methyl group. A hypomethylating agent (or demethylating agent[1]) is a drug that inhibits DNA methylation. Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, hypomethylating agents are considered a type of epigenetic therapy.

Currently available hypomethylating agents block the activity of DNA methyltransferase (DNA methyltransferase inhibitors / DNMT inhibitors). Currently two members of the class, azacitidine and decitabine are FDA-approved for use in the United States in myelodysplastic syndrome and are being investigated for use in a number of tumors.[2]

Clinical use

Two hypomethylating agents are approved for the treatment of myelodysplastic syndrome by the United States FDA[3][4]

Mechanism of action

DNA methylation is the modification of DNA nucleotides by addition of a methyl group. These methyl groups are associated with changes in the ability of the corresponding DNA to be used. Patterns of DNA methylation are stable during cellular division. Excessive methylation of tumor suppressor genes in some cancers contributes to the growth and survival of the cancer. Hypomethylating agents decrease the amount of cellular DNA methylation and disrupt these patterns.[9]

See also

References



Latest research - Hypomethylating agent

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