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.
Quantifying CDK inhibitor selectivity in live cells.
Wells CI. et al, (2020), Nature communications, 11
Deep analysis of the USP18-dependent ISGylome and proteome unveils important roles for USP18 in tumour cell antigenicity and radiosensitivity
Pinto-Fernandez A. et al, (2020)
Quantifying Target Occupancy of Small Molecules Within Living Cells.
Robers MB. et al, (2020), Annual review of biochemistry
Importance of Quantifying Drug-Target Engagement in Cells
Stefaniak J. and Huber KVM., (2020), ACS Medicinal Chemistry Letters
Re-evaluating the mechanism of action of α,β-unsaturated carbonyl DUB inhibitors b-AP15 and VLX1570: a paradigmatic example of unspecific protein crosslinking with Michael acceptor motif-containing drugs.
Ward JA. et al, (2020), Journal of Medicinal Chemistry