M. Schirle

Reinstating targeted protein degradation with DCAF1 PROTACs in CRBN PROTAC resistant settings

This study develops DCAF1-based PROTACs to overcome CRBN resistance in targeted protein degradation, demonstrating effective degradation of BTK in CRBN-resistant cells.

Ophiobolin A Covalently Targets Complex IV Leading to Mitochondrial Metabolic Collapse in Cancer Cells

This study identifies Ophiobolin A's covalent targets in complex IV of mitochondria, revealing a mechanism of metabolic collapse and cell death in cancer cells.

Targeted Protein Degradation through E2 Recruitment

This study identifies a covalent recruiter for the E2 ubiquitin conjugating enzyme UBE2D, enabling targeted protein degradation via PROTACs.

Rational Chemical Design of Molecular Glue Degraders

This paper develops a strategy to convert protein-targeting ligands into molecular glue degraders by identifying a covalent handle that induces proteasome-mediated degradation of target proteins.

Chemoproteomics-Enabled Discovery of a Covalent Molecular Glue Degrader Targeting NF-κB

This study identifies a covalent molecular glue degrader, EN450, that induces the degradation of NFKB1 via a ternary complex with UBE2D, leading to anti-proliferative effects in leukemia cells.

Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors

This study identifies and optimizes potent pyrazoline-based covalent inhibitors of SARS-CoV-2 Mpro, showing activity against multiple coronaviruses.

Deubiquitinase-Targeting Chimeras for Targeted Protein Stabilization

This paper introduces the DUBTAC platform for targeted protein stabilization by linking a covalent OTUB1 recruiter to lumacaftor, demonstrating stabilization of ΔF508-CFTR in human cells.

Discovery of a Covalent FEM1B Recruiter for Targeted Protein Degradation Applications

The paper discovers a covalent ligand, EN106, that targets FEM1B for PROTAC-based protein degradation, demonstrating its utility in degrading BRD4.

Chemoproteomics Enabled Discovery of Selective Probes for NuA4 Factor BRD8

The paper identifies a novel interaction between BRD8 and the NuA4 complex using chemoproteomics and develops selective probes for BRD8.

A Nimbolide-Based Kinase Degrader Preferentially Degrades Oncogenic BCR-ABL

This paper develops a PROTAC molecule, BT1, that selectively degrades BCR-ABL over c-ABL in leukemia cells using nimbolide as an E3 ligase recruiter, showing additional anti-proliferative effects.

Manumycin Polyketides Act as Molecular Glues Between UBR7 and P53 to Impair Breast Cancer Pathogenicity

The paper identifies manumycin polyketides as molecular glues that bind UBR7 and P53, impairing breast cancer pathogenicity through p53 activation and cell death.

Harnessing the Anti-Cancer Natural Product Nimbolide for Targeted Protein Degradation

This study identifies nimbolide's mechanism of action by showing it targets RNF114, leading to stabilization of p21 and inhibition of breast cancer cell proliferation.

Covalent Ligand Screening Uncovers a RNF4 E3 Ligase Recruiter for Targeted Protein Degradation Applications

This study identifies a covalent ligand for RNF4, an E3 ligase, and demonstrates its use in designing a bifunctional degrader that effectively degrades BRD4.