C. Arrowsmith

Discovery of a cell-active chikungunya virus nsP2 protease inhibitor using a covalent fragment-based screening approach

This paper identifies and characterizes RA-0002034, a covalent inhibitor of CHIKV nsP2 protease, showing potent inhibition and selectivity against alphaviruses.

Epigenetic vulnerabilities of leukemia harboring inactivating EZH2 mutations

This study identifies epigenetic vulnerabilities in AML and MDS/MPN with EZH2 mutations, showing increased sensitivity to EZH2 and EED inhibitors and upregulation of cell death pathways.

Chemical Tools for the Gid4 Subunit of the Human E3 Ligase C-terminal to LisH (CTLH) Degradation Complex

The paper develops chemical tools and probes for the Gid4 subunit of the human CTLH E3 ligase complex, achieving sub-100 nM binding affinity for further study.

Recruitment of FBXO22 for Targeted Degradation of NSD2

This paper describes a targeted protein degradation strategy using UNC8732 to recruit FBXO22 for NSD2 degradation, leading to growth suppression and reversal of drug resistance in leukemia cells.

Probing the mechanism of Cbl-b inhibition by a small-molecule inhibitor

The paper investigates how a small-molecule inhibitor binds to and inactivates Cbl-b, revealing a structural mechanism that locks the protein in an inactive conformation.

RAS and PP2A activities converge on epigenetic gene regulation

This study identifies epigenetic gene regulation as a convergence point for RAS hyperactivity and PP2A inhibition in cancer, showing their co-regulation of key chromatin modifiers and oncogenic transcription.

cGAS recruitment to micronuclei is dictated by pre-existing nuclear chromatin status.

The paper shows that cGAS recruitment to micronuclei depends on pre-existing nuclear chromatin status, not just MN envelope rupture.

Structure Activity Relationship of USP5 Allosteric Inhibitors

This paper develops a chemical series of USP5 allosteric inhibitors, identifies a selective compound with structural and functional characterization.

Design, Synthesis and Evaluation of WD-repeat containing protein 5 (WDR5) degraders

This study designs, synthesizes, and evaluates two series of WDR5 degraders, showing that linker length and nature affect degradation efficacy.

Rational Design and Synthesis of Selective PRMT4 Inhibitors: a New Chemotype for Development of Cancer Therapeutics

This study designs and synthesizes a new class of selective PRMT4 inhibitors with improved selectivity over other PRMT family members.

A semi-automated intestinal organoid screening method demonstrates epigenetic control of epithelial differentiation

This study develops a semi-automated intestinal organoid screening method to identify epigenetic regulators of epithelial differentiation, finding that inhibiting type I PRMTs enhances differentiation and blocks adenoma growth.

Identification and Characterization of the First Fragment Hits for SETDB1 Tudor Domain

The paper identifies small molecule fragments that bind to the tudor domain of SETDB1 and describes their binding modes and biophysical properties.

Design and characterisation of mutant and wild-type huntingtin proteins produced from a toolkit of scalable eukaryotic expression systems

This paper develops a toolkit for producing mutant and wild-type huntingtin proteins in eukaryotic systems to enable biochemical and structural studies of HD-related mutations.

Identification and Structure-Activity Relationship of HDAC6 Zinc-finger Ubiquitin Binding Domain Inhibitors

The paper identifies HDAC6 ZnF-UBD inhibitors and describes their structure-activity relationships, revealing key binding features and potential for further optimization.