Zielproteins

Zielproteins, or target proteins, are proteins that serve as the primary molecular targets for therapeutic interventions. They are chosen because modulating their activity or expression can influence disease-related pathways and outcomes. Zielproteins are often enzymes, receptors, transporters, ion channels, or transcription factors that participate in signaling networks or metabolic processes. The concept of Zielproteins guides drug discovery by focusing on proteins whose inhibition, activation, or degradation is predicted to yield a therapeutic benefit while maintaining acceptable safety.

Before a Zielprotein becomes a drug target, its relevance to disease must be demonstrated, usually through genetic perturbation studies showing that altering the protein affects disease phenotypes, and through assessments of druggability, meaning the protein has a binding site accessible to small molecules or biologics and that modulation is feasible in physiological conditions.

Identification and validation employ diverse approaches: high-throughput genetic screens (CRISPR, RNAi) to reveal dependencies; proteomics and chemoproteomics to map interactions; structural biology to assess binding pockets; and computational methods to prioritize candidates.

Once validated, Zielproteins inform lead discovery and development of various modalities, including small-molecule inhibitors, monoclonal antibodies, biologics, or gene-editing strategies. Examples include kinase targets in cancer, GPCRs in metabolism or sensation, and receptors in immuno-oncology.

Challenges include redundancy and compensation, resistance development, tissue-specific expression, and safety concerns from on-target toxicity. The heterogeneity of diseases and patient-specific factors also complicate target choice and clinical success.

The term is widely used in pharmacology and precision medicine to organize drug discovery around the proteins most central to disease mechanisms.