| Literature DB >> 25248678 |
Duncan Shaw1, Greg Hollingworth2, Nicolas Soldermann3, Elizabeth Sprague4, Walter Schuler3, Eric Vangrevelinghe3, Nicholas Duggan2, Matthew Thomas2, Takatoshi Kosaka2, Nigel Waters2, Maurice J van Eis5.
Abstract
A novel class of selective inhibitors of ROCK1 and ROCK2 has been identified by structural based drug design. PK/PD experiments using a set of highly selective Rho kinase inhibitors suggest that systemic Rho kinase inhibition is linked to a reversible reduction in lymphocyte counts. These results led to the consideration of topical delivery of these molecules, and to the identification of a lead molecule 7 which shows promising PK and PD in a murine model of pulmonary hypertension after intra-tracheal dosing.Entities:
Keywords: Inhibitors; Intra-tracheal dosing; Lymphocyte depletion; Pulmonary arterial hypertension; Rho kinase
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Year: 2014 PMID： 25248678 DOI： 10.1016/j.bmcl.2014.09.002
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823