Enzyme Inhibitors
Enzymes are among the most validated drug target classes. We pursue selective inhibitors across therapeutic areas, guided by structural data and SAR, with applications ranging from cancer to neurodegeneration to skin disorders.
Inhibitors of FAHD1 — Toward New Targets in Cancer and Aging
FAH domain containing protein 1 (FAHD1) is a mitochondrial oxaloacetate decarboxylase that regulates TCA cycle flux and has emerged as a key factor in cellular senescence and cancer cell survival. In collaboration with Alexander Weiss (University of Innsbruck) and building on first-generation inhibitors developed with our mentor Hubert Gstach, we are designing next-generation small molecules targeting FAHD1 as potential tools to probe mitochondrial metabolism and as candidates for anti-cancer applications. Our synthetic efforts are guided by high-resolution X-ray structures of the enzyme and structure–activity relationships from published inhibitor scaffolds.
FAHD1 inhibitor discovery — from mitochondrial target to structure-guided drug design.
Tyrosinase Inhibitors
Tyrosinase is a copper-containing enzyme central to melanin biosynthesis, and its dysregulation is implicated in hyperpigmentation disorders, melanoma, and neurodegenerative processes in Parkinson's disease. Our group designs and synthesizes small-molecule tyrosinase inhibitors based on cinnamic acid and cinnamoyl amide scaffolds, exploring structure–activity relationships through systematic variation of aromatic substitution patterns. This work has yielded promising inhibitory activities in the low micromolar range against mushroom tyrosinase (Agaricus bisporus). In collaboration with partners at the University of Messina, we are advancing toward validation against human tyrosinase. Our broader interest in the field is reflected in a comprehensive review of heterocyclic tyrosinase inhibitors (Int. J. Mol. Sci. 2023).
Tyrosinase inhibition — from mushroom enzyme to therapeutic applications in skin and brain disorders.
GABA-A Receptor Modulators
GABA-A receptors are pentameric ligand-gated ion channels central to inhibitory neurotransmission, and their subtypes represent attractive targets for neurological and psychiatric disorders. Our group synthesizes and optimizes small-molecule modulators with subtype-selective profiles, guided by computational docking and validated through electrophysiology. Current efforts aim to develop tool compounds and potential therapeutic leads with improved selectivity.
GABA-A receptor