The Drug Discovery, Chemical Biology and Screening platform offers services to enable world-class research in chemical biology. Services include drug discovery & chemical biology process guidance and advice, assay development, high throughput and high content screening, chemoinformatics, follow-up assays, in vitro ADMET and connections to organic/medicinal chemistry.
Assay development and optimization is often a bottleneck in drug discovery and chemical biology so we provide this support, both in terms of hands-on support as well as guidance and access to the best possible instrumentation and technologies.
Assay development starts by identifying the target and its activity. The next step is determining whether the objective is to inhibit or activate the target. A great starting point for assay development is a bench scale assay for the target used by the principal investigator, who initiates the small molecule screen by contacting the Drug Discovery, Chemical Biology and Screening platform. A small molecule chemical screen can be cell-based or based on a biochemical assay. The assay developers of the platform set up the assay and optimize it for high throughput screening.
If you want to initiate a new project at the FIMM High Throughput Biomedicine Unit or Faculty of Pharmacy and need support in assay development and optimization, please fill the contact form.
We maintain many collections of chemical libraries and house instruments needed to process large amounts of samples in high throughput fashion. Our platforms include plate-based screening of cells and biochemical screens. We support both plate reader assays and high content microscopy.
More information about Chemical Screening done at the FIMM High Throughput Biomedicine unit: https://www.fimm.fi/en/services/technology-centre/htb/htb-services/chemi...
More information about screening facilities at the Faculty of Pharmacy: Bioactivity Screening Unit
Example of a chemical/cell-based assay workflow:
In our Drug Sensitivity and Resistance Testing (DSRT), a set of clinically relevant and targeted bioactive compounds are tested in a dose response series against patient-derived primary cancer cells or cell-lines, after which responses, typically in the form of DSS:s are calculated for each drug. The standard DSRT assay consists, to date, of 527 drugs in 5 concentrations, on 8 384-well plates. The standard readout in an DSRT assay is cell viability and cell death, but microscopic readouts are also offered.
Watch our video about Drug Sensitivity and Resistance Testing here.
Example of a DSRT workflow is shown here:
- Hit analoging, SAR, secondary screens, compound QC, prediction of in vivo properties for POC
- ADME-T and adverse effect predictive modelling
- Assay expertise at the participating partner sites bring capacity to support users in follow-up testing beyond screening to take screening hits towards a proof-of-principle compound
- In particular, Faculty of Pharmacy offers world-class expertise in in vitro and in silico pharmacological profiling of compounds
- The Drug Discovery, Chemical Biology and Screening platform offers cherry-picking of hit compounds by chemoinformatics from the national chemical collection and confirmatory testing at screening sites, making follow-up testing affordable to the user.
- Chemoinformatics support for hit compound evaluation and optimization
- Pharmaceutical big data collection and integration
- A compound collection comprising more than 140 000 synthetic drug-like chemicals, natural products and clinical drugs is provided to the users.
- Automated nanoscale dispensing systems allows for the users to access the compounds as part of pre-defined or in user-defined sets.
- A collection of drugs and state-of-the-art bioactive tool compounds is also available one-at-a-time or in small subsets for biologists interested an affordable source for best-in-class inhibitors and other bioactives. This service will be further enhanced by adding on a biologics collection of drugs and bioactive macromolecules.
The FIMM chemical libraries are listed here.
- Faculty of Pharmacy also provides the capacity and expertise to validate integrity, stability and metabolism of chemicals by liquid chromatography mass spectrometry (LC-MS)
- LC-MS measurements for small molecules and peptides
- Available instruments are UPLC triple quadrupole for quantitative analysis and UPLC q-tof for compound identification
- The core maintains the Ambion Silencer Select V4-library and houses instruments needed to process a large amount of samples in high throughput fashion.
- Our platforms enable genome-wide, sub-library or candidate gene screens.
More information about RNAi Screening done at the FIMM High Throughput Biomedicine unit: https://www.fimm.fi/en/services/technology-centre/htb/htb-services/rnai-...
Example of a RNAi screening workflow: