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Journal Article
Research Support, Non-U.S. Gov't
Xanthone derivatives as phosphoglycerate mutase 1 inhibitors: Design, synthesis, and biological evaluation.
Bioorganic & Medicinal Chemistry 2018 May 2
Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that dynamically converts 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG), which was upregulated to coordinate glycolysis, pentose phosphate pathway (PPP) and serine biosynthesis to promote cancer cell proliferation and tumor growth in a variety of cancers. However, only a few inhibitors of PGAM1 have been reported with poor molecular or cellular efficacy. In this paper, a series of xanthone derivatives were discovered as novel PGAM1 inhibitors through scaffold hopping and sulfonamide reversal strategy based on the lead compound PGMI-004A. Most xanthone derivatives showed higher potency against PGAM1 than PGMI-004A and exhibited moderate anti-proliferation activity on different cancer cell lines.
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