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.
HTB maintains a collection of about 140 000 small molecule compounds including known drugs, bioactives, and diversified sets of chemicals. The drugs and known bioactives are ideal for biological profiling, drug repositioning and personalized medicine-type of screens, while the larger chemical diversity collections are best suited for molecular probe discovery.
HTB also houses instruments needed to process large amounts of samples in high throughput fashion. Our platforms are well suited for biochemical and cell-based screening using multi-well plates. We support both plate reader assays and high content microscopy.
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 a Drug Sensitivity Scores (DSS) are calculated for each drug. The standard DSRT assay consists, to date, of 527 drugs in 5 concentrations, on eight 384-well plates. The standard readout in a DSRT assay is cell viability (CellTiter Glow, CTG) and cell death (CellTox Green, CTxG). Flow cytometry and microscopic readouts are also offered.
Flow cytometry -based drug screening assay provides cell population-specific drug response data.
- The platform allows to study the activity and mechanism of action of approved and investigational drugs and to learn about cell vulnerabilities and drug resistance mechanisms.
- Samples are typically biobanked frozen or freshly isolated mononuclear cells from hematological malignancies or cell lines.
- We use drugs or drug candidates and cell surface markers of your choice. See contact details below.
- Oncology collection QA1B has 40 clinically relevant drugs and combinations in seven doses on a 384-well plate. QA1B is designed for acute myeloid leukemia and acute lymphoblastic leukemia. Other drug collections are available.
- Optimized antibody panels to detect main cell types of AML and ALL contain up to 9 cell surface markers and viability dyes.
- Efficient and economical use of detection antibodies is achieved using ECHO acoustic dispenser for accurately transferring small volumes of reagents and other lab automation for antibody staining.
- Drug response data is reported using a web-based service (TDB).
Read more about FIMM HTB high throughput flow-cytomery services here.
With questions concerning HT flow cytometry contact Tanja Ruokoranta.
- 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
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.
- 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.
- High Throughput Biomedicine Unit provides assay-ready drug plates for those customers who need to run their assays in their own laboratory.
- Customers may choose either an existing drug set from our collections or cherry-pick selected drugs.
- Drugs are placed into assay plates using our ultrasound-driven ECHO dispencers and may be stored at low oxygen and humidity under nitrogen gas in storage pods for several months.
- Sealed plates can be sent to remote locations by post.
Read more 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 a full genome Ambion Silencer Select V4-library of siRNAs 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. We support both plate reader assays (luminescence, fluorescence, absorbance) and high content microscopy. We also provide expertise in assay development and optimization.
More information about RNAi Screening at the FIMM High Throughput Biomedicine unit can be found here.