C.H. Arrowsmith

The paper shows that BAY-805 induces USP21-KLHL12 association, recruiting USP21 to COPII vesicles and impairing large cargo transport.

This study shows HAI-2 inactivates TTSPs only after zymogen activation, revealing a novel mechanism for regulating these proteases and suggesting therapeutic applications.

The paper maps over 20,000 human protein-protein interactions mediated by short linear motifs using a peptide library screening approach.

The paper uses high-throughput affinity-selection mass spectrometry to identify protein targets of ToxCast and PFAS compounds, discovering novel interactions and revealing distinct binding patterns of legacy and replacement PFAS.

The paper measures conformational fluctuations of protein domains using hydrogen-deuterium exchange mass spectrometry and uses computational modeling to design mutations that stabilize low-stability segments.

This paper reveals the structural basis of NSD2 degradation via SCF-FBXO22 recruitment, showing how aldehyde-based degraders induce conformational changes for covalent binding and efficient protein degradation.

The paper tests PROTACs targeting FBXO22 and finds no degradation of four targets but identifies potent FBXO22 homo-PROTACs and CRBN/VHL-mediated degraders.

The paper develops a chemical probe targeting the USP16 zinc-finger ubiquitin-binding domain and evaluates its selectivity and activity in cellular assays.

The paper shows that glioblastoma stem cells form spatial patterns correlated with their transcriptional state, using image analysis to link morphology and gene expression.

This study introduces E-ASMS, a method to detect weak binders and assess enantioselectivity, identifying 16 binders across 12 human protein targets with confirmed binding mechanisms.

The paper identifies a small molecule ligand for the HTT-HAP40 complex using AS-MS and validates its binding through multiple techniques, highlighting a druggable interface for HD therapeutics.

This study identifies Cathepsin K as a key host protease for SARS-CoV-2 spike activation and shows it can be inhibited by existing drugs.

This paper introduces ProtacID, a BioID-based method to identify PROTAC-proximal proteins, validates degradation targets, and identifies non-productive interactions in human cells.

The paper describes the enantioselective resolution of a chemical probe targeting CHIKV nsP2 helicase, showing potent antiviral activity for one enantiomer and low activity for the other.

The paper determines the structural basis of TMPRSS11D autocleavage activation and shows that nafamostat mesylate is cleaved by TMPRSS11D, reducing its efficacy as a protease inhibitor.

This paper identifies and optimizes oxaspiropiperidine inhibitors targeting nsP2hel, showing nanomolar antiviral activity against multiple alphaviruses.

The paper identifies UNC10013, a covalent ligand targeting SETDB1's 3TD domain, which reduces methyltransferase activity and shows selectivity in cells.

The paper evaluates computational hit-finding methods for targeting the WDR domain of LRRK2, a Parkinson's disease protein, finding that diverse strategies yielded weakly potent compounds.

The paper develops a resource for discovering ligands for WDR proteins using experimental and computational methods, leading to the identification of drug-like ligands for 9 out of 20 targets.

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

The paper identifies a deficient PAR response in Huntington disease patients, suggesting a potential therapeutic target for early intervention.

This study identifies huntingtin as an RNA-binding protein that interacts with G-rich RNA sequences, including those in the NEAT1 paraspeckle lncRNA.

The paper curates a database of helicase inhibitors, Heli-SMACC, and tests selected compounds against SARS-CoV-2 NSP13 ATPase, finding twelve inhibitors with dose-response activity.

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.

The paper introduces PFI-7, a chemical probe that inhibits GID4 Pro/N-degron interactions, revealing non-degradative roles of the CTLH complex in human cells.

This paper identifies PRMT5 as a regulator of HTT mRNA splicing and alternative polyadenylation, showing that its inhibition reduces full-length HTT protein levels by promoting premature termination and cleavage.

The paper shows that the CTLH E3 ligase complex regulates substrate selectivity and autoregulation by exchanging its β-propeller subunits WDR26 and muskelin.

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.

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.

The paper shows that (R,R)-59, a SETDB1 ligand, enhances SETDB1-mediated methylation of Akt1 and promotes cell proliferation.