Lei Jin

TL;DR: These compounds bind to the SIRT1 enzyme–peptide substrate complex at an allosteric site amino-terminal to the catalytic domain and lower the Michaelis constant for acetylated substrates and improve whole-body glucose homeostasis and insulin sensitivity in adipose tissue, skeletal muscle and liver.

TL;DR: In vivo administration of EPZ004777 leads to extension of survival in a mouse MLL xenograft model, providing compelling support for DOT1L inhibition as a basis for targeted therapeutics against MLL.

TL;DR: The discovery of EPZ005687 is reported, a potent inhibitor of EZH2 that reduces H3K27 methylation in various lymphoma cells; this translates into apoptotic cell killing in heterozygous Tyr641 or Ala677 mutant cells, with minimal effects on the proliferation of wild-type cells.

TL;DR: The characterization of EPZ-5676 is described, a potent and selective aminonucleoside inhibitor of DOT1L histone methyltransferase activity that demonstrates 37 000-fold selectivity over all other methyltransferases tested.

TL;DR: EPZ015666 is an orally available inhibitor of PRMT5 enzymatic activity in biochemical assays with a half-maximal inhibitory concentration (IC50) of 22 nM and broad selectivity against a panel of other histone methyltransferases.