期刊
ACS MEDICINAL CHEMISTRY LETTERS
卷 8, 期 12, 页码 1252-1257出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.7b00312
关键词
autotaxin; IPF; LPA; tool compound
In an effort to find new therapeutic interventions addressing the unmet medical need of patients with idiopathic pulmonary fibrosis, we initiated a program to identify new autotaxin (ATX) inhibitors. Starting from a recently published compound (PF-8380), we identified several highly potent ATX inhibitors with improved pharmacokinetic and safety profiles. Further optimization efforts resulted in the identification of a single-digit nanomolar lead compound (BI-2545) that shows substantial lowering of LPA in vivo and is therefore considered a valuable tool for further studies.
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