Kyle D. Konze
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View article: Targeting EZH2 and PRC2 dependence as novel anticancer therapy
Targeting EZH2 and PRC2 dependence as novel anticancer therapy Open
Distinctive patterns of chromatin modification control gene expression and define cellular identity during development and cell differentiation. Polycomb repressive complex 2 (PRC2), the sole mammalian enzymatic complex capable of establis…
View article: A chemical tool for chemiprecipitation of the lysine methyltransferase, G9a, in vitro and in vivo
A chemical tool for chemiprecipitation of the lysine methyltransferase, G9a, in vitro and in vivo Open
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. Importantly, UNC0965 maintains high in vitro …
View article: An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1
An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1 Open
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 repressive post-translational modification…
View article: Combining Cloud-Based Free Energy Calculations, Synthetically Aware Enumerations and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization
Combining Cloud-Based Free Energy Calculations, Synthetically Aware Enumerations and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization Open
The hit identification process usually involves the profiling of millions to more recently billions of compounds either via traditional experimental high throughput screens (HTS) or computational virtual high throughput screens (vHTS). We …
View article: Combining Cloud-Based Free Energy Calculations, Synthetically Aware Enumerations and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization
Combining Cloud-Based Free Energy Calculations, Synthetically Aware Enumerations and Goal-Directed Generative Machine Learning for Rapid Large-Scale Chemical Exploration and Optimization Open
The hit identification process usually involves the profiling of millions to more recently billions of compounds either via traditional experimental high throughput screens (HTS) or computational virtual high throughput screens (vHTS). We …
View article: Chemical Probes for the Lysine Methyltransferases EZH2 and G9a: Design, Development, and Application
Chemical Probes for the Lysine Methyltransferases EZH2 and G9a: Design, Development, and Application Open
In eukaryotic genomes, DNA is wrapped around histone proteins to form repeating units known as nucleosomes, which are further condensed into chromosomes. This high level of structure creates a barrier to transcription, which is maintained …
View article: 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
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 Open
The hit-to-lead and lead optimization processes usually involve the design, synthesis, and profiling of thousands of analogs prior to clinical candidate nomination. A hit finding campaign may begin with a virtual screen that explores milli…
View article: Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors
Multi-omic Dissection of Oncogenically Active Epiproteomes Identifies Drivers of Proliferative and Invasive Breast Tumors Open
Proliferative and invasive breast tumors evolve heterogeneously in individual patients, posing significant challenges in identifying new druggable targets for precision, effective therapy. Here we present a functional multi-omics method, i…
View article: 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
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 Open
We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and…
View article: 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
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 Open
We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and…
View article: 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
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 Open
We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and…
View article: 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
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 Open
We report a new computational technique, PathFinder, that uses retrosynthetic analysis followed by combinatorial synthesis to generate novel compounds in synthetically accessible chemical space. Coupling PathFinder with active learning and…
View article: Structure–Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors
Structure–Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors Open
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 and/or hypertrimethylation of H3K27 are assoc…