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.
Open resources for chemical probes and their implications for future drug discovery.
Balıkçı E. et al, (2023), Expert Opin Drug Discov, 18, 505 - 513
Discovery of a chemical probe to study implications of BPTF bromodomain inhibition in cellular and in vivo experiments.
Martinelli P. et al, (2023), ChemMedChem
Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4.
Londregan AT. et al, (2023), J Med Chem, 66, 460 - 472
Cyclic peptides target the aromatic cage of a PHD-finger reader domain to modulate epigenetic protein function
Coleman OD. et al, (2023), Chemical Science
Global Assessment of Drug Target Engagement and Selectivity of Covalent Cysteine-Reactive Inhibitors Using Alkyne-Functionalized Probes.
Rothweiler EM. and Huber KVM., (2023), Methods Mol Biol, 2706, 191 - 200