A5092190114- Protein Degradation and Inhibitors
- Peptidase Inhibition and Analysis
- Semiconductor materials and devices
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Virus-based gene therapy research
- Click Chemistry and Applications
- Polymer Nanocomposite Synthesis and Irradiation
- Polymer Nanocomposites and Properties
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
University of Zurich
2024-2025
École Polytechnique Fédérale de Lausanne
2023
ETH Zurich
2023
Proteolysis Targeting Chimeras (PROTACs) are bifunctional molecules that simultaneously bind an E3 ligase and a protein of interest, inducing degradation the latter via ubiquitin-proteasome system. Here we present development degraders targeting CREB-binding (CBP) E1A-associated (EP300)─two homologous multidomain enzymes crucial for enhancer-mediated transcription. Our PROTAC campaign focused on CPI-1612, reported inhibitor histone acetyltransferase (HAT) domain these two proteins. A novel...
Bromodomain adjacent to zinc finger 2A and 2B (BAZ2A BAZ2B) are homologous proteins that serve as regulatory subunits in different initiation switch complexes. Despite their structural similarity, BAZ2A/B seem play roles disease development. However, reported inhibitors bind similarly both homologues. Here we report the discovery of dBAZ2 dBAZ2B, first-in-class Proteolysis Targeting Chimeras (PROTACs) degrading BAZ2B, respectively. induces degradation with a D max ≥ 97% (BAZ2A_DC50 = 180 nM;...
PROteolysis TArgeting Chimeras (PROTACs) is a highly promising class of therapeutic agents that degrade target proteins through catalytic, event-driven mechanism. However, their broad activity and lack tissue selectivity can lead to on-target toxicities off-site in healthy tissues, limiting clinical potential. To address this, we developed novel two-tier selective PROTAC prodrug 1, specifically targets prostate cancer (PCa), based on the well-established BRD4 degrader MZ1. Compound 1...
Tumor Necrosis Factor α (TNF-α) is an inflammatory cytokine that a key mediator in autoimmune disorders such as Crohn’s disease and rheumatoid arthritis (RA). Targeting epigenetic regulators of transcription signaling promising therapeutic approach. However, the specific mechanisms by which they contribute to immune response are not well established yet. Here, we present new class selective CBP/EP300-bromodomain (BRD) inhibitors comprising 3-methylcinnoline acetyl-lysine mimic discovered...
Here we present the development of dCE-2, a structurally novel PROTAC targeting CREB-binding protein (CBP) and E1A-associated (EP300) – two homologous multidomain enzymes crucial for enhancer-mediated transcription. The design dCE-2 was based on crystal structure an in-house bromodomain (BRD) inhibitor featuring as acetyl-lysine mimic 3-methyl cinnoline discovered by high-throughput fragment docking. Our study shows that, despite its modest binding affinity to CBP/EP300-BRD, remarkable...
The number of diabetic patients is rising globally and concomitantly so do the diabetes associated complications. gut secretes a variety proteins to control blood glucose levels and/or food intake. As drug class GLP-1 agonists based on secreted peptide positive metabolic effects bariatric surgery are at least partially mediated by peptides, we were interested in other which have yet be explored. In this respect identified protein FAM3D analyzing sequencing data from L- epithelial cells VSG...
We present the development of