This paper introduces a degron decoy system that uses pathological seeding to clear multimeric α-synuclein by co-aggregating with oligomers and enabling degradation via a small molecule trigger.

bioRxiv · Feb 24, 2026 · PreprintPharmacology & Toxicology

ZBTB11 Depletion Targets Metabolic Vulnerabilities in K-Ras Inhibitor Resistant PDAC

Nathan L. Tran, Jiewei Jiang, Mengyao Ma, Gillian E. Gadbois, Kevin Christian Montecillo Gulay, Alyssa L. Verano, Cara R. Schiavon, Elena Rebollo, Haowen Zhou, Chun‐Teng Huang, Rabi Murad, David A. Scott, Uri Manor, Anne G. Bang, Hervé Tiriac, , Fleur M. Ferguson

This study develops ZBTB11 degraders to target metabolic vulnerabilities in K-Ras inhibitor-resistant PDAC, showing improved anti-cancer activity with reduced toxicity to neurons.

Nature Chemical Biology · Aug 11, 2025Peer-reviewedCancer Biology

A Lipid Prodrug Strategy Enhances Targeted Protein Degrader CNS Pharmacokinetics

Georges A. Leconte, Gillian E. Gadbois, Yadira J Sepulveda, Ady Schwarz, Erin Chang, Raymond T. Suhandynata, Jeremiah D. Momper, Fleur M. Ferguson

This study identifies fatty acid promoieties that improve CNS exposure of targeted protein degraders by enhancing pharmacokinetics and BBB permeability.

Journal of Medicinal Chemistry · Aug 5, 2025Peer-reviewedPharmacology & Toxicology

A Kinetic Scout Approach Accelerates Targeted Protein Degrader Development

Angela T. Fan, Gillian E. Gadbois, Hai‐Tsang Huang, Charu Chaudhry, Jiewei Jiang, Logan H. Sigua, Emily R. Smith, Sitong Wu, Grace J. Poirier, Kara Dunne-Dombrink, Pavitra Goyal, Andrew J. Tao, William R. Sellers, Eric S. Fischer, Katherine A. Donovan, Fleur M. Ferguson

This study develops a kinetic scout approach to accelerate targeted protein degrader development by tuning ligand residence time through chemical proteomics and mechanistic assays.

Angewandte Chemie International Edition · Nov 27, 2024Peer-reviewedPharmacology & Toxicology