EPZ004777

Ligand id: 7377

Name: EPZ004777

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 11
Hydrogen bond donors 5
Rotatable bonds 12
Topological polar surface area 150.79
Molecular weight 539.32
XLogP 3.8
No. Lipinski's rules broken 2

Molecular properties generated using the CDK

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].