M. Schapira

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.

Drug Discovery in Low Data Regimes: Leveraging a Computational Pipeline for the Discovery of Novel SARS-CoV-2 Nsp14-MTase Inhibitors

This paper introduces a computational pipeline for identifying SARS-CoV-2 nsp14 inhibitors using virtual screening, identifying seven candidates including NSC620333 and SS148, with experimental validation of binding affinity and structural insights.

Small molecule screen identifies non-catalytic USP3 chemical handle

The paper identifies a small molecule ligand for the ZnF-UBD of USP3 with a KD of 14 µM, which could serve as a starting point for developing DUBTACs.

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.

A combinatorial anticancer drug screen identifies off-target effects of epigenetic chemical probes

This study identifies epigenetic chemical probes that enhance TAK-243 cytotoxicity via off-target ABCG2 inhibition and develops a cell-based assay to measure ABCG2 inhibition.

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.

Discovery of small molecule antagonists of human Retinoblastoma Binding Protein 4 (RBBP4)

This study identifies small molecule antagonists of RBBP4's top pocket, competes with protein and histone interactions, and reports the first crystal structure of RBBP4 with a small molecule.

Structure, Mechanism and Crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase

This study presents crystal structures of SARS-CoV-2 NSP13 and identifies druggable pockets, revealing potential targets for antiviral drug development through fragment screening.

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.

HAP40 orchestrates huntingtin structure for differential interaction with polyglutamine expanded exon 1

This study reveals how HAP40 orchestrates HTT structure, affecting its interaction with polyglutamine-expanded exon 1, providing insights into Huntington's disease mechanisms.

The SARS-CoV-2 replication-transcription complex is a priority target for broad-spectrum pan-coronavirus drugs

The paper identifies two highly conserved druggable sites in the SARS-CoV-2 replication-transcription complex as potential targets for broad-spectrum antiviral drugs.

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.

Probing the SAM Binding Site of SARS-CoV-2 nsp14 in vitro Using SAM Competitive Inhibitors Guides Developing Selective bi-substrate Inhibitors

This paper identifies SAM competitive inhibitors of SARS-CoV-2 nsp14 methyltransferase and characterizes their mechanism, guiding the development of selective bi-substrate inhibitors.

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.

Negative controls of chemical probes can be misleading

This paper shows that negative controls for chemical probes can be unreliable, as they may fail to inhibit off-targets, leading to misleading conclusions about gene-phenotype associations.

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.

Discovery of small molecule antagonists of the USP5 zinc finger ubiquitin-binding domain

The paper identifies small molecule antagonists targeting the USP5 ZnF-UBD, providing a framework for developing chemical probes to study its role in ubiquitin signaling.

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.

A Systematic Analysis Of Atomic Protein-Ligand Interactions In The PDB

The paper analyzes atomic protein-ligand interactions in the PDB, finding that hydrophobic interactions are common in high-efficiency ligands while polar interactions are over-represented in fragment inhibitors.