BIH Chemical Biology Platform
The BIH Chemical Biology Platform provides support in high-throughput profiling of biological probes, cellular reporter systems or purified components like enzymes. This high-throughput enables to screen ten thousands of probes for either identification of small molecule drug-like compounds (60.000 cpds) which modulate biological functions or for genome-wide RNA interference to study protein functions. Beside of compound activity profiling the established HTS detection systems may also profile biological probes from biobanks established at BIH.
Moreover this support is complemented by a Medicinal Chemistry group (headed by Marc Nazaré), which enables either for chemical optimization of primary hits to early leads by improving the overall characteristics and profile such as activity, selectivity, solubility and stability or for development of chemical probes to be used for diagnostic means.
The small molecule drug-like screening collection contain about 3.000 FDA approved drugs and drugs in clinical trials suitable for drug repurposing approaches plus about 30.000 World-Drug-Index derived compounds and 20.000 natural product derived compounds from Analyticon Discovery.
he Screening Unit operates since 2004 and established High-Content Screening with automated microscopes, with FLIPR-Tetra System for high-speed kinetics by cellular imaging plus reader based detections of fluorescence and luminescence to be used for enzyme screens (kinases, phosphatases, metabolic enzymes…).
Project support is only restricted by assay acceptance test for HTS, because two negative results within a test of ten positive probes results in 20% randomized hits, which means 12.000 false negatives (hits) by screening 60.000 compounds (about 30 true hits expectation). Therefore we also support assay optimization for HTS before screening. The small-molecule screening collection is managed by fully automated interface KIWI/REMP stores and its quality is secured by several parameters (LC-MS/UV/fluorescence, solubility measurement and cytotox proifiling in different cell lines).
The involvement of Medicinal Chemistry should be regarded as a long term commitment and collaboration: in most cases > 6 months by support of at least one scientist. Hit optimization is enabled by state-of-the art laboratory equipment for solution-phase chemistry, parallel synthesis and automated purification systems (HPLC, LC-MS, NP-chromatography). The available support is offered on the basis of a previous assessment of the hit to increase the likelihood of a successful outcome of the investigation, and to estimate the potential for chemical optimization.
We offer training in our labs for all scientists interested in HTS and automated data processing.