A Selective Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Chronic Obstructive Pulmonary Disease (COPD): Discovery of (S)-2-(8-(Methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408)
A Selective Matrix Metalloprotease 12 Inhibitor for Potential Treatment of Chronic Obstructive Pulmonary Disease (COPD): Discovery of (S)-2-(8-(Methoxycarbonylamino)dibenzo[b,d]furan-3-sulfonamido)-3-methylbutanoic acid (MMP408)
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DOI：
10.1021/jm900093d
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发表时间：
2009-04-09
影响因子：
7.3
通讯作者：
Mansour, Tarek S.
中科院分区：
文献类型：
--
作者：
Li, Wei;Li, Jianchang;Mansour, Tarek S.
基质金属蛋白酶12在气道炎症和重塑中起重要作用。在COPD患者的肺中发现MMP-12的表达和产生增加。MMP 408（14）是一种有效的选择性MMP-12抑制剂，通过先导优化从有效的基质金属蛋白酶2和13抑制剂衍生而来，具有良好的物理性质和生物利用度。该化合物在小鼠模型中阻断rhMMP-12诱导的肺部炎症，并进一步开发用于治疗COPD。
Matrix metalloprotease 12 plays a significant role in airway inflammation and remodeling. Increased expression and production of MMP-12 have-been found in the lung of human COPD patients. MMP408 (14), a potent and selective MMP-12 inhibitor, was derived from a potent matrix metalloprotease 2 and 13 inhibitor via lead optimization and has good physical properties and bioavailability. The compound blocks rhMMP-12-induced lung inflammation in a mouse model and was advanced for further development for the treatment of COPD.