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Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo.

ABSTRACT: 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.

SUBMITTER: Kuttruff CA

PROVIDER: S-EPMC5733304 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Discovery of BI-2545: A Novel Autotaxin Inhibitor That Significantly Reduces LPA Levels in Vivo.

Kuttruff Christian A CA Ferrara Marco M Bretschneider Tom T Hoerer Stefan S Handschuh Sandra S Nosse Bernd B Romig Helmut H Nicklin Paul P Roth Gerald J GJ

ACS medicinal chemistry letters 20171108 12

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 ...[more]

PMID: 29259743

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