RRC ID 51271
Author Yin C, Fufa T, Chandrasekar G, Aeluri M, Zaky V, Abdelhady S, Rodríguez AB, Jakobsson J, Varnoosfaderani FS, Mahalingam J, Liu J, Larsson O, Hovatta O, Gaunitz F, Göndör A, Andäng M, Kitambi SS.
Title Phenotypic Screen Identifies a Small Molecule Modulating ERK2 and Promoting Stem Cell Proliferation.
Journal Front Pharmacol
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.
Volume 8
Pages 726
Published 2017-10-24
DOI 10.3389/fphar.2017.00726
PMID 29114221
PMC PMC5660848
IF 4.225
Times Cited 1
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