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An orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and EZH1.
EZH2 or EZH1 is the catalytic subunit of the polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). The trimethylation of H3K27 (H3K27me3) is a transcriptionally… Expand
Selective inhibition of EZH2 and EZH1 enzymatic activity by a small molecule suppresses MLL-rearranged leukemia.
Enhancer of zeste homolog 2 (EZH2) and related EZH1 control gene expression and promote tumorigenesis via methylating histone H3 at lysine 27 (H3K27). These methyltransferases are ideal therapeutic… Expand
Selective Inhibitors of Protein Methyltransferases
Mounting evidence suggests that protein methyltransferases (PMTs), which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and human… Expand
Targeting EZH2 and PRC2 dependence as novel anticancer therapy.
Distinctive patterns of chromatin modification control gene expression and define cellular identity during development and cell differentiation. Polycomb repressive complex 2 (PRC2), the sole… Expand
A Chemical Tool for In Vitro and In Vivo Precipitation of Lysine Methyltransferase G9a
Here we report the design, synthesis, and biochemical characterization of a new chemical tool, UNC0965. UNC0965 is a biotinylated version of our previously reported G9a chemical probe, UNC0638.… Expand
Polycomb genes, miRNA, and their deregulation in B-cell malignancies.
Posttranslational modifications of histone proteins represent a fundamental means to define distinctive epigenetic states and regulate gene expression during development and differentiation.… Expand
Structure-Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors.
EZH2 or EZH1 (enhancer of zeste homologue 2 or 1) is the catalytic subunit of polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 lysine 27 (H3K27). PRC2 hyperactivity… Expand
Reaction-Based Enumeration, Active Learning, and Free Energy Calculations To Rapidly Explore Synthetically Tractable Chemical Space and Optimize Potency of Cyclin-Dependent Kinase 2 Inhibitors
- Kyle D. Konze, P. H. Bos, +6 authors Sathesh Bhat
- Computer Science, Chemistry
- J. Chem. Inf. Model.
- 12 August 2019
The hit-to-lead and lead optimization processes usually involve the design, synthesis, and profiling of thousands of analogs prior to clinical candidate nomination. Expand
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors
Summary Proliferative and invasive breast tumors evolve heterogeneously in individual patients, posing significant challenges in identifying new druggable targets for precision, effective therapy.… Expand
Combining Cloud-Based Free-Energy Calculations, Synthetically Aware Enumerations, and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization
- Phani Ghanakota, P. H. Bos, +6 authors Sathesh Bhat
- Computer Science, Medicine
- J. Chem. Inf. Model.
- 2 June 2020
We combine large scale enumeration and cloud-based FEP profiling with goal-directed generative machine learning, which results in a higher enrichment of potent compounds over previously described approaches, and can rapidly accelerate the discovery of novel chemical matter within a predefined potency and property space. Expand