Challenging drug targets require creative ideas, novel concepts, and often the integration of multiple technologies to enable the development of new therapeutic modalities. In the Pomplun Lab, we embrace this challenge by creating innovative drug discovery platforms that combine rational design with combinatorial chemistry to uncover novel chemical modalities capable of addressing therapeutically relevant biomolecules.
Combinatorial drug discovery: The identification of novel bioactive molecules is fundamental for any drug discovery campaign. We develop combinatorial synthesis procedures for drug-like chemical modalities. Compound libraries with millions of members are used to identify high affinity ligands to therapeutically relevant targets. Smart library design strategies enable the decoding of hit compounds by mass spectrometry. Drug targets investigated by the Pomplun Lab include transcription factors, non-coding RNAs and viral proteins. Researchers involved in this research line develop novel combinatorial synthesis procedures, develop high throughput assays and use experimental and computational medicinal chemistry technologies for hit-to-lead optimization.
Rational drug design and hit-to-lead optimization: Beyond early discovery, our lab is deeply invested in turning hits (coming from our own screenings or collaboration projects) into optimized leads. We build on classical medicinal chemistry, but push the field forward by developing new tools such as computer-aided drug design workflows, automated synthesis platforms, and combinatorial optimization strategies. For especially tough targets like protein–protein interactions, we pioneer covalent approaches to boost potency and selectivity, opening up opportunities where traditional methods fall short.
Synthetic transcription factors: At the interface of chemistry, biology, and precision medicine lies the challenge of creating synthetic molecules that can enter cells and precisely regulate gene expression. In this research line, we design chemical modalities that target specific DNA sequences to activate or block transcription. Our synthetic transcription factors are engineered to be cell-penetrating and stable, enabling both chemistry-driven optimization and biological applications to control gene expression in disease-relevant contexts.
Pomplun Lab 