Stefan Knapp

This paper develops a miniaturized traceless Staudinger ligation method to rapidly discover potent BRD4-targeting PROTACs by screening crude reaction mixtures directly in biological assays.

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

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.

This paper elucidates the structural mechanisms by which LRRK2 is activated and autoinhibited, showing how mutations affect these processes and suggesting therapeutic strategies.

The paper maps over 20,000 human protein-protein interactions mediated by short linear motifs using a peptide library screening approach.

This paper introduces kinetic fingerprints to evaluate KIT inhibitors, showing that residence time and dissociation rates predict clinical success and resistance.

This paper compares the effects of USP7 inhibition and degradation in cancer cells, finding distinct phenotypic and proteomic responses.

This study identifies NMD inhibition as a therapeutic strategy for SCLC by enhancing immunogenicity and improving immunotherapy efficacy through increased neoantigen presentation.

This paper introduces TRIPs, neomorphic molecules that recruit BAF complexes to rewire BCL6 in DLBCL, inducing apoptosis through chromatin remodeling.

The paper reports the design, synthesis, and characterization of new ULK1/2 inhibitors that inhibit autophagy and upregulate MHC I in NSCLC cells, supporting their potential as cancer therapeutics.

This paper introduces a miniaturized PROTAC synthesis workflow that bypasses compound purification, enabling rapid screening and degradation assessment of multiple targets.

This study introduces E-ASMS, a method to detect weak binders and assess enantioselectivity, identifying 16 binders across 12 human protein targets with confirmed binding mechanisms.

The paper evaluates peptidomimetic inhibitors using a set of complementary assays to support drug discovery.

This study develops peptide-based tracers for SPSB2 E3 ligase by conjugating cell-penetrating peptides to degrons, enabling efficient cellular delivery and target engagement assessment.

The paper identifies inhibitor-induced kinase destabilization as a common phenomenon and reveals that it occurs through endogenous proteolytic mechanisms rather than classical ubiquitination.

This study shows that the RNF4 ligand CCW16 induces ferroptosis in AML cells through a RNF4-independent mechanism by causing covalent protein modifications and upregulating ferroptosis markers.

The paper describes the optimization of a macrocyclic scaffold to develop a selective STK10 inhibitor with nanomolar activity and good kinome selectivity.

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

The paper develops pyrazolopyrimidine-based macrocyclic kinase inhibitors targeting AAK1, showing selectivity over related NAK family members and antiviral activity against RNA viruses.

This study develops a covalent LIMK1 inhibitor that selectively targets a unique cysteine, enabling isoform-specific studies of LIMK1 function.

This paper designs and tests sEH-PROTACs to degrade soluble epoxide hydrolase, identifying PROTAC 23 as effective in degrading sEH in human macrophages.

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.

This study develops heterobifunctional protein binders that selectively kill specific cell types by leveraging the abundance of FKBP12, demonstrating enhanced efficacy through cellular enrichment.

The paper repurposes a benzoxazepinone scaffold originally designed for RIPK1 inhibition to develop a novel type-III LIMK1/2 inhibitor with high selectivity.

The paper evaluates diverse ubiquitin pathway inhibitors as controls for CRBN and VHL-mediated protein degradation, assessing their potency and toxicity using the HiBiT system and high content assays.

This paper develops a miniaturized Direct-to-Biology platform for rapid PROTAC degrader synthesis and screening, identifying potent sEH degraders with subnanomolar activity.

The paper evaluates the druggability of LC3/GABARAP for autophagy modulators and identifies ligands that bind to the HP2 pocket of the LIR docking site.

The paper optimizes a 2-aminopyrimidine-based macrocycle to create a dual EPHA2/GAK kinase inhibitor with antiviral activity against dengue virus.

The paper designs and evaluates chemical linchpins targeting CK2α with a novel binding mode combining allosteric and ATP competitive elements, showing high selectivity and low micromolar activity.

This study develops a high-affinity DARPin that binds to LRRK2's WD40 domain, improving structural analysis and revealing its role in disrupting LRRK2 filaments and Rab8A phosphorylation.