Synonyms: EPZ 004777 | EPZ-004777
Compound class:
Synthetic organic
Comment: EPZ004777 is an analogue of the enzyme co-factor S-adenosyl methionine (SAM). SAM is the classical methyl donor for methyltrasferases.
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
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No information available. |
Mechanism Of Action and Pharmacodynamic Effects |
EPZ004777 inhibits histone methylation (at H379K) by DOT1L. The histone lysine methyltransferase DOT1L has been shown to be involved in the development and maintenance of MLL-rearranged leukemias [1]; rearrangement of the MLL gene and abberant methylation of lysine 79 of histone H3 are associated with some leukemias [1,3]. Treatment with EPZ004777 causes cell death and tumour regression in cell and animal models containing MLL rearrangements [2]. EPZ004777 is >1000-fold selective for DOT1L compared to other histone lysine methyltransferases tested [2]. |