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Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX).

ABSTRACT: Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA's role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX.

SUBMITTER: East JE

PROVIDER: S-EPMC2975792 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Synthesis and structure-activity relationships of tyrosine-based inhibitors of autotaxin (ATX).

East James E JE Kennedy Andrew J AJ Tomsig Jose L JL De Leon Alexandra R AR Lynch Kevin R KR Macdonald Timothy L TL

Bioorganic & medicinal chemistry letters 20100915 23

Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA's role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX. ...[more]

PMID: 20951039

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