M. Szewczyk

A resource to enable chemical biology and drug discovery of WDR Proteins

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.

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 DCAF12 interactions with MAGEA3 and CCT5 C-terminal degrons

This study characterizes DCAF12 interactions with MAGEA3 and CCT5 degrons using biophysical assays and cryo-EM, revealing key residues for degron recognition and informing PROTAC design.

Communication between wolf and domestic dog revealed from experimental scent marking

This study investigates how wolves respond to scent marks from domestic dogs and other wolves, finding that wolves react more to unfamiliar wolf scent marks and that juveniles are more affected by dog scent marks.

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.

Discovery and characterization of a chemical probe targeting the zinc-finger ubiquitin-binding domain of HDAC6

The paper identifies and characterizes a chemical probe, SGC-UBD253, that targets the HDAC6 UBD with selectivity, and a less active derivative as a negative control.

Reference compounds for characterizing cellular injury in high-content cellular morphology assays

The paper profiles 218 cytotoxic and nuisance compounds in U-2 OS cells to create reference compounds for improving assay optimization and compound prioritization in cellular morphology assays.

PRMT7 ablation stimulates anti-tumor immunity and sensitizes melanoma to immune checkpoint blockade

This study shows PRMT7 inhibition enhances anti-tumor immunity and improves response to immune checkpoint blockade in melanoma by modulating immune cell infiltration and PD-L1 expression.

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.

Pharmacological targeting of a PWWP domain demonstrates cooperative control of NSD2 localization

The paper develops a chemical probe, UNC6934, that targets the PWWP1 domain of NSD2, revealing cooperative control of NSD2 localization through chromatin reader domains.

A First-in-class, Highly Selective and Cell-active AllostericInhibitor of Protein Arginine Methyltransferase 6 (PRMT6)

This paper reports the discovery of a first-in-class, highly selective allosteric inhibitor of PRMT6, SGC6870, with potent activity and selectivity in vitro and in cells.

Discovery of Small-Molecule Antagonists of the PWWP Domain of NSD2

This study identifies small-molecule antagonists of the NSD2 PWWP domain that block its interaction with H3K36me2, providing a tool for further investigation of NSD2's role in disease.

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 Chemical Probe of CARM1 Alters Epigenetic Plasticity against Breast Cancer Cell Invasion

This study identifies SKI-73 as a CARM1 chemical probe that reduces breast cancer cell invasion by altering epigenetic plasticity, distinct from CARM1 knockout effects.