High-throughput screening for modulators of cellular contractile force

When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signaling intermediates with poorly defined relationship to such a physiological endpoint. Using cellular force a...

Full description

Saved in:
Bibliographic Details
Published in:arXiv.org 2014-11
Main Authors: Chan Young Park, Zhou, Enhua H, Tambe, Dhananjay, Chen, Bohao, Lavoie, Tera, Dowell, Maria, Simeonov, Anton, Maloney, David J, Marinkovic, Aleksandar, Tschumperlin, Daniel J, Burger, Stephanie, Frykenberg, Matthew, Butler, James P, Stamer, W Daniel, Johnson, Mark, Solway, Julian, Fredberg, Jeffrey J, Ramaswamy Krishnan
Format: Article
Language:English
Subjects:
Asthma
Endothelial cells
Glaucoma
Modulators
Muscles
Screening
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:When cellular contractile forces are central to pathophysiology, these forces comprise a logical target of therapy. Nevertheless, existing high-throughput screens are limited to upstream signaling intermediates with poorly defined relationship to such a physiological endpoint. Using cellular force as the target, here we screened libraries to identify novel drug candidates in the case of human airway smooth muscle cells in the context of asthma, and also in the case of Schlemm's canal endothelial cells in the context of glaucoma. This approach identified several drug candidates for both asthma and glaucoma. We attained rates of 1000 compounds per screening day, thus establishing a force-based cellular platform for high-throughput drug discovery.
ISSN:2331-8422