Axcelead DDP and FUJIFILM Cellular Dynamics, Inc. support your drug discovery using iCell® Products
iPSC-derived cell types are useful physiologically relevant models of human diseases.
Recently, compounds discovered in phenotypic screening using iPSC-derived cells have been shown to be effective in clinical trials, thus making the use of iPSC-derived cells for drug screening an attractive approach.
Axcelead DDP supports your drug discovery from assay development through high-throughput screening using iPSC-derived cells from FUJIFILM Cellular Dynamics, Inc. (FCDI), a leading company of iPSC technologies.
Axcelead DDP Phenotypic Screening Services
Utilizing the scientific experiences of Axcelead DDP and FCDI, we offer a wide selection of phenotypic screening services incorporating iCell®＊ Products.
*For more information about the various iCell Products from FUJIFILM Cellular Dynamics available for Screening Services, visit here
Our capabilities support you throughout your screening process:
- We can lead your drug discovery efforts using FCDI’s iPSC technology and a wide range of screening experiences of Axcelead DDP.
- We can propose the best screening strategies according to your needs from assay development to HTS execution.
- Our vast library of pharma origin with high quality and diverse structures increases your chances in finding hit compounds.
For example, you can use this service in the following situations!
A Variety of Assays and Experiences in Phenotypic Screening
Case study
Screening for Phagocytosis Modulators using iCell® Microglia AD TREM2
Goal
To discover phagocytosis activators using iCell® Microglia AD TREM2 homozygous knockout (iCell Microglia TREM2 HO）cells.
Background
Mutations in the transmembrane protein, TREM2, has become a research focus because of its role in the binding and clearance of Aβ oligomers, thus making it a potential risk factor of Alzheimer’s disease. Elucidation of the mechanism would be useful for development of therapies for Alzheimer’s disease.
Assay Development
A biologically annotated compound library, consisting of about 3,400 compounds, was tested in a phagocytosis assay using iCell Microglia TREM2 HO to screen for phagocytosis activators.
Compound concentration for the primary screening was set at 3 µM.
Assay Development Results
We optimized an assay to evaluate cellular uptake activity of fluorescent-labeled Aβ in a 384-well format using InCuCyte® ZOOM. Results showed Aβ uptake kinetics in iCell Microglia TREM2 HO was slower than that of iCell Microglia (wild type, WT).
Screening Cascade Outline
Primary Screen Results
After the primary screening step, false-positive compounds (e.g., auto-fluorescence, cell toxic, and others) were removed. Based on the activity distribution from the primary screening, positive compounds were selected for a following screening cascade, reproducibility assay and concentration-response assay.
Correlation between Aβ uptake activity and cytotoxicity in the primary screening
Correlation between Aβ uptake activity and cytotoxicity in the primary screening
Dose Response Results
We successfully identified several phagocytosis activators. These compounds enhanced phagocytosis activity without severe cytotoxicity.
Representative compounds, A and B, increased the phagocytosis activity in iCell Microglia TREM2 HO comparable to levels of iCell Microglia. Compound A enhanced phagocytosis activity in both iCell Microglia and iCell Microglia TREM2 HO, while compound B increased it only in iCell Microglia TREM2 HO, suggesting that these compounds modulated phagocytosis activity through different mode-of–actions.
Axcelead DDP Phenotypic Screening Services
Our vast experience in phenotypic screening combined with our diverse compound libraries provides high-quality phenotypic screening services.
High-throughput screening capability for Phenotypic drug discovery
