Chemical Biology - Drug Discovery - Proteomics - Systems Pharmacology - Medicinal Chemistry
Probing Biology with Small Molecules for Drug Target Discovery
The development of new medicines to treat diseases like cancer or inflammatory disorders is dependent on the identification of novel drug targets. Target selection requires an understanding of the functional relevance of a given protein in both physiological and pathophysiological conditions.
Chemical Biology combines chemistry and biology to generate small molecule tools, so-called “chemical probes”, that enable the functional exploration of cellular proteins with regard to their relevance for drug discovery. Candidate targets may originate from genetic studies linking the expression or mutation of a selected gene to a particular disease, in vitro genetic screens such as RNA-interference or genome-editing (e.g. CRISPR), compounds identified in phenotypic assays or drugs already in use.
To identify, explore and validate targets the Huber laboratory uses a variety of different discovery approaches such as small molecule screens, biochemical assays, protein X-ray crystallography, chemical and protein-protein interaction proteomics, medicinal chemistry, RNAi, genome-editing alongside classical molecular and cellular biology techniques aiming at the development of chemical probes that may provide leads for drug discovery.
Covalent fragment-based ligand screening approaches for identification of novel ubiquitin proteasome system modulators
Rothweiler EM. et al, (2022), Biological Chemistry, 403, 391 - 402
A chemical biology toolbox to investigate in-cell target engagement and specificity of PRMT5-inhibitors
Rothweiler EM. et al, (2022)
Chemoproteomic Profiling of Covalent XPO1 Inhibitors to Assess Target Engagement and Selectivity
Martin JG. et al, (2021), ChemBioChem, 22, 2116 - 2123
Fragment Screening Reveals Starting Points for Rational Design of Galactokinase 1 Inhibitors to Treat Classic Galactosemia
Mackinnon SR. et al, (2021), ACS Chemical Biology
TP-MAP - an Integrated Software Package for the Analysis of 1D and 2D Thermal Profiling Data
Feyertag F. and Huber KVM., (2021)