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

Autor:	Kuttruff CA; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Ferrara M; Boehringer Ingelheim Research Italia S.a.s. di BI IT S.r.l., Via G. Lorenzini 8, 20139 Milano, Italy., Bretschneider T; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Hoerer S; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Handschuh S; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Nosse B; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Romig H; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Nicklin P; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany., Roth GJ; Medicinal Chemistry, Drug Discovery Sciences, and Immunology & Respiratory, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach an der Riss, Germany.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2017 Nov 08; Vol. 8 (12), pp. 1252-1257. Date of Electronic Publication: 2017 Nov 08 (Print Publication: 2017).
DOI:	10.1021/acsmedchemlett.7b00312
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest.
Databáze:	MEDLINE
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