Structure-based Rational Drug Development

Example of an early drug candidate that has been developed using structure-based drug discovery to target an important protein-protein interaction in cancer. The small molecule inhibitor is shown as stick model, the target protein as surface representatio

The structure-based drug design enables the rational design of lead compounds. The atomic-resolution structures are used to guide the design. Structure-based methodology has contributed to the development of many therapeutic agents, such as Inhibitors of HIV protease, Abl kinase (Imatinib) or Bcl-2 proteins.

X-ray crystallography and NMR spectroscopy are used here to determine the structure of the target protein, identify pharmacophores and obtain structure-activity relationship data. Active molecules are found by in silico screening or de novo design. Hits from high-throughput screens (HTS) (e. g, based on in vitro binding assays such as fluorescence polarization, AlphaScreen, etc.) are validated by crystallographic analysis and NMR. Fragment-based screening by NMR is established at HMGU and FMP. In the network of Helmholtz centres (HMGU, HZI, FZJ, MDC/FMP) a unique and international competitive infrastructure and expertise is available to support structural biology and structure-based drug discovery.

 

Coordinator

  • Prof. Dr. Michael Sattler

    Institute of Structural Biology

    Helmholtz Zentrum München – German Research Center for Environmental Health

    Ingolstädter Landstraße 1
    85764 Neuherberg

    Phone: +49 89 3187-3800
    Fax: +49 89 3187-193800
    E-Mail: Contact

Scientists

Ulrike Uhrig, EMBL

Hartmut Oschkinat und
Ronald Kühne, FMP

Birgit Strodel und
Dieter Willbold, FZJ

Ana Messias, HGMU/TUM

Dirk Heinz, Cristiane Ritter
und Rolf Hartmann, HZI/HIPS

Udo Heinemann, MDC