h-1152 and Hypertension--Pulmonary

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.

Topics: Animals; Crystallography, X-Ray; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypertension, Pulmonary; Mice; Mice, Inbred BALB C; Models, Molecular; Molecular Structure; Protein Kinase Inhibitors; Rats; Rats, Inbred Lew; rho-Associated Kinases; Structure-Activity Relationship