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Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma.
TLDR
It is shown that certain mono- and polyunsaturated fatty acids bind directly to PPARalpha and PPARgamma at physiological concentrations, and that the eicosanoids 8(S)-hydroxyeicosatetraenoic acid and 15-deoxy-Delta12,14-prostaglandin J2 can function as subtype-selective ligands for PPAR alpha and PPARS, respectively.
Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ
TLDR
Evidence that PPARs serve as physiological sensors of lipid levels is provided and a molecular mechanism whereby dietary fatty acids can modulate lipid homeostasis is suggested.
A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.
TLDR
UNC0638 is reported, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets, and markedly reduced the clonogenicity of MCF7 cells and disproportionately affected several genomic loci encoding microRNAs.
An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1.
TLDR
UNC1999 was the first orally bioavailable inhibitor that has high in vitro potency for wild-type and mutant EZH2 as well as EzH1, a closely related H3K27 methyltransferase that shares 96% sequence identity with EZh2 in their respective catalytic domains.
Catalytic site remodelling of the DOT1L methyltransferase by selective inhibitors.
TLDR
The three-dimensional structure of the protein methyl transferase DOT1L bound to EPZ004777, the first S-adenosylmethionine-competitive inhibitor of a protein methyltransferase with in vivo efficacy, and those of four new analogues reveal remodelling of the catalytic site.
Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP.
TLDR
The discovery of the first G9a and GLP in vivo chemical probe UNC0642, which not only maintains high in vitro and cellular potency, low cell toxicity, and excellent selectivity, but also displays improved in vivo PK properties, making it suitable for animal studies.
Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia
TLDR
It is shown that C/EBPα p30, but not the normal p42 isoform, preferentially interacts with Wdr5, a key component of SET/MLL histone-methyltransferase complexes, and OICR-9429 is a novel small-molecule antagonist of the Wdr 5-MLL interaction.
A Potent, Selective, and Cell-Active Inhibitor of Human Type I Protein Arginine Methyltransferases.
TLDR
The discovery of a potent, selective, and cell-active inhibitor of human type I PRMTs, MS023, and characterization of this inhibitor in a battery of biochemical, biophysical, and cellular assays are reported.
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