Requirements for Using iPSC-Based Cell Models for Assay Development in Drug Discovery

Author(s):  
Klaus Christensen ◽  
Filip Roudnicky ◽  
Christoph Patsch ◽  
Mark Burcin

2013 ◽  
Vol 27 (1) ◽  
pp. 17-27 ◽  
Author(s):  
Wenwei Liu ◽  
Yaguang Deng ◽  
Ying Liu ◽  
Wenrong Gong ◽  
Wenbin Deng




2017 ◽  
Vol 177 ◽  
pp. 32-43 ◽  
Author(s):  
Sandy S.C. Hung ◽  
Shahnaz Khan ◽  
Camden Y. Lo ◽  
Alex W. Hewitt ◽  
Raymond C.B. Wong


Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1629 ◽  
Author(s):  
Johannes Ottl ◽  
Lukas Leder ◽  
Jonas V. Schaefer ◽  
Christoph E. Dumelin

The scope of targets investigated in pharmaceutical research is continuously moving into uncharted territory. Consequently, finding suitable chemical matter with current compound collections is proving increasingly difficult. Encoded library technologies enable the rapid exploration of large chemical space for the identification of ligands for such targets. These binders facilitate drug discovery projects both as tools for target validation, structural elucidation and assay development as well as starting points for medicinal chemistry. Novartis internalized two complementing encoded library platforms to accelerate the initiation of its drug discovery programs. For the identification of low-molecular weight ligands, we apply DNA-encoded libraries. In addition, encoded peptide libraries are employed to identify cyclic peptides. This review discusses how we apply these two platforms in our research and why we consider it beneficial to run both pipelines in-house.



2012 ◽  
Vol 15 (1) ◽  
pp. 3-14 ◽  
Author(s):  
Chong Shen ◽  
Liang Zhang ◽  
Guoliang Zhang ◽  
Qin Meng


2021 ◽  
pp. 107883
Author(s):  
Daniel Simão ◽  
Catarina M. Gomes ◽  
Paula M. Alves ◽  
Catarina Brito


Pharmaceutics ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 176 ◽  
Author(s):  
Laura Hellinen ◽  
Heidi Hongisto ◽  
Eva Ramsay ◽  
Kai Kaarniranta ◽  
Kati-Sisko Vellonen ◽  
...  

The retinal pigment epithelial (RPE) cell monolayer forms the outer blood–retinal barrier and has a crucial role in ocular pharmacokinetics. Although several RPE cell models are available, there have been no systematic comparisons of their barrier properties with respect to drug permeability. We compared the barrier properties of several RPE secondary cell lines (ARPE19, ARPE19mel, and LEPI) and both primary (hfRPE) and stem-cell derived RPE (hESC-RPE) cells by investigating the permeability of nine drugs (aztreonam, ciprofloxacin, dexamethasone, fluconazole, ganciclovir, ketorolac, methotrexate, voriconazole, and quinidine) across cell monolayers. ARPE19, ARPE19mel, and hfRPE cells displayed a narrow Papp value range, with relatively high permeation rates (5.2–26 × 10−6 cm/s. In contrast, hESC-RPE and LEPI cells efficiently restricted the drug flux, and displayed even lower Papp values than those reported for bovine RPE-choroid, with the range of 0.4–32 cm−6/s (hESC-RPE cells) and 0.4–29 × 10−6 cm/s, (LEPI cells). Therefore, ARPE19, ARPE19mel, and hfRPE cells failed to form a tight barrier, whereas hESC-RPE and LEPI cells restricted the drug flux to a similar extent as bovine RPE-choroid. Therefore, LEPI and hESC-RPE cells are valuable tools in ocular drug discovery.





2011 ◽  
Vol 17 (9) ◽  
pp. 475-484 ◽  
Author(s):  
Richard P. Davis ◽  
Cathelijne W. van den Berg ◽  
Simona Casini ◽  
Stefan R. Braam ◽  
Christine L. Mummery


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