Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension
Novel ROCK inhibitors for the treatment of pulmonary arterial hypertension
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DOI：
10.1016/j.bmcl.2014.09.002
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发表时间：
2014-10-15
影响因子：
2.7
通讯作者：
van Eis, Maurice J.
中科院分区：
文献类型：
--
作者：
Shaw, Duncan;Hollingworth, Greg;van Eis, Maurice J.
基于结构的药物设计已鉴定出一类新的ROCK1和ROCK2选择性抑制剂。使用一组高选择性Rho激酶抑制剂的PK/PD实验表明，系统性Rho激酶抑制与淋巴细胞计数的可逆减少有关。这些结果导致考虑局部递送这些分子，并鉴定了一种先导分子7，该分子在气管内给药后在小鼠肺动脉高压模型中显示出有希望的PK和PD。(C) 2014 Elsevier Ltd.版权所有。
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. (C) 2014 Elsevier Ltd. All rights reserved.