Title |
Phenotypic Screen Identifies a Small Molecule Modulating ERK2 and Promoting Stem Cell Proliferation
|
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Published in |
Frontiers in Pharmacology, October 2017
|
DOI | 10.3389/fphar.2017.00726 |
Pubmed ID | |
Authors |
Chang Yin, Temesgen Fufa, Gayathri Chandrasekar, Madhu Aeluri, Verina Zaky, Shaimaa Abdelhady, Antonio B. Rodríguez, Johan Jakobsson, Farzaneh Shahin Varnoosfaderani, Jayashri Mahalingam, Jianping Liu, Olle Larsson, Outi Hovatta, Frank Gaunitz, Anita Göndör, Michael Andäng, Satish S. Kitambi |
Abstract |
Stem cells display a fundamentally different mechanism of proliferation control when compared to somatic cells. Uncovering these mechanisms would maximize the impact in drug discovery with a higher translational applicability. The unbiased approach used in phenotype-based drug discovery (PDD) programs can offer a unique opportunity to identify such novel biological phenomenon. Here, we describe an integrated phenotypic screening approach, employing a combination of in vitro and in vivo PDD models to identify a small molecule increasing stem cell proliferation. We demonstrate that a combination of both in vitro and in vivo screening models improves hit identification and reproducibility of effects across various PDD models. Using cell viability and colony size phenotype measurement we characterize the structure activity relationship of the lead molecule, and identify that the small molecule inhibits phosphorylation of ERK2 and promotes stem cell proliferation. This study demonstrates a PDD approach that employs combinatorial models to identify compounds promoting stem cell proliferation. |
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Geographical breakdown
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United States | 1 | 20% |
Switzerland | 1 | 20% |
Unknown | 3 | 60% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 80% |
Scientists | 1 | 20% |
Mendeley readers
Geographical breakdown
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 8 | 35% |
Student > Bachelor | 2 | 9% |
Student > Ph. D. Student | 2 | 9% |
Student > Master | 1 | 4% |
Professor > Associate Professor | 1 | 4% |
Other | 1 | 4% |
Unknown | 8 | 35% |
Readers by discipline | Count | As % |
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Engineering | 3 | 13% |
Agricultural and Biological Sciences | 3 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
Chemistry | 1 | 4% |
Other | 1 | 4% |
Unknown | 9 | 39% |