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.
Cite
@article{arxiv.1411.5695,
title = {High-throughput screening for modulators of cellular contractile force},
author = {Chan Young Park and Enhua H. Zhou and Dhananjay Tambe and Bohao Chen and Tera Lavoie and Maria Dowell and Anton Simeonov and David J. Maloney and Aleksandar Marinkovic and Daniel J. Tschumperlin and Stephanie Burger and Matthew Frykenberg and James P. Butler and W. Daniel Stamer and Mark Johnson and Julian Solway and Jeffrey J. Fredberg and Ramaswamy Krishnan},
journal= {arXiv preprint arXiv:1411.5695},
year = {2014}
}