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Azacitidine is a chemical analogue of the nucleoside cytidine, which is present in DNA and RNA.It is thought to have antineoplastic activity via two mechanisms – at low doses, by inhibiting of DNA methyltransferase, causing hypomethylation of DNA, [16] and at high doses, by its direct cytotoxicity to abnormal hematopoietic cells in the bone marrow through its incorporation into DNA and RNA ...
There is very little known about the mechanism of action of these drugs. However, it was shown in 2015 that a possible mechanism of action of these drugs in colorectal cancer-initiating cells is through activating dsRNA expression which leads to the activation of the MDA5/MAVS RNA recognition pathway inducing some sort of viral mimicry inside the cell.
Decitabine (i.e., 5-aza-2′-deoxycytidine), sold under the brand name Dacogen among others, acts as a nucleic acid synthesis inhibitor. [4] It is a medication for the treatment of myelodysplastic syndromes , a class of conditions where certain blood cells are dysfunctional, and for acute myeloid leukemia (AML). [ 5 ]
A hypomethylating agent (or demethylating agent [1]) is a drug that inhibits DNA methylation: the modification of DNA nucleotides by addition of a methyl group.Because DNA methylation affects cellular function through successive generations of cells without changing the underlying DNA sequence, treatment with a hypomethylating agent is considered a type of epigenetic therapy.
The DNA methylation inhibitor, 5-azacytidine is also known to promote phenotypic transdifferentiation of cardiac cells to skeletal myoblasts. [23] In prostate cancer, treatment with androgen receptor targeted therapies induces neuroendocrine transdifferentiation in a subset of patients.
2.5 Histone deacetylase inhibitors: Panobinostat: add: add: add: add Romidepsin: IV: Histone deacetylase inhibitor, hence inducing alterations in gene expression in the affected cells. Peripheral and cutaneous T cell lymphoma. Electrolyte anomalies, anaemia, thrombocytopenia, neutropenia, lymphopenia and ECG anomalies. Valproate [Note 1] PO, IV ...
The recognition of epigenetic changes in DNA structure in MDS has explained the success of two (namely the hypomethylating agents 5-azacytidine and decitabine) of three (the third is lenalidomide) commercially available medications approved by the U.S. Food and Drug Administration to treat MDS.
Epigenetic priming refers to a latent epigenetic state triggered by stimuli, such as a drug or environmental changes. The epigenetically primed state is characterized by chromatin loosening, which is the change of chromatin state from heterochromatin (tightly bound and inaccessible) to euchromatin (loosely bound and fully accessible), which leads to an increased transcription of certain genes ...