This study identifies cyanoquinoline-based HIPK4 inhibitors with nanomolar potency and reveals their cell-type-specific effects on HIPK4 proteostasis and autophagy.

Journal of the American Chemical Society · Oct 5, 2026Peer-reviewedBiochemistry

Macrocyclization of Broad-Spectrum Kinase Inhibitor Bosutinib leads to Potent and Selective Quinoline-based HIPK4 Inhibitor AZ137

Athina Zerva, Nicolai D. Raig, Zaile Zhuang, Andreas Kraemer, Johannes Dopfer, Riley K. Togashi, Martin P. Schwalm, Lewis Elson, Julia Marie Frischkorn, Benedict‐Tilman Berger, Susanne Müller, James Chen, Stefan Knapp, Thomas Hanke

The paper describes the development of AZ137, a potent and selective HIPK4 inhibitor derived from bosutinib, and validates its utility as a tool for studying HIPK4's biological functions.

Journal of Medicinal Chemistry · Aug 18, 2026Peer-reviewedBiochemistry

Proteome-wide impact of LRRK1 and 2 inhibitors on protein interactions and phosphorylation

Jasmin Jansen, Marcel Wendel, Nicolai D. Raig, Tom Kraus, Katherine J. Surridge, Swetha Mahesula, Nicole Richter-Muller, Sebastian Mathea, Samara L. Reck‐Peterson, Stefan Knapp, Florian Stengel

This study uses proximity labeling and phosphoproteomics to analyze LRRK1 and LRRK2 interactomes and phosphorylation sites, identifying novel substrates and the impact of inhibitors.

bioRxiv · Sep 3, 2025 · PreprintMolecular Biology

Type-II kinase inhibitors that target Parkinson's Disease-associated LRRK2

Nicolai D. Raig, Katherine J. Surridge, Marta M. Sanz Murillo, Verena Dederer, Andreas Krämer, Martin P. Schwalm, Nicholas M. Lattal, Lewis Elson, Deep Chatterjee, Sebastian Mathea, Thomas Hanke, Andrés E. Leschziner, Samara L. Reck‐Peterson, Stefan Knapp

Hybrid type-II inhibitors RN277 and RN341 target inactive LRRK2 with far fewer kinase off-targets than Rebastinib, preserve S935 phosphorylation, and rescue kinesin motility in vitro.

Science Advances · Jun 6, 2025Peer-reviewedCell Biology✦ In-depth digest