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Xanthine derivatives inhibit FTO in an L-ascorbic acid-dependent manner
Kamui Tanaka1, Akiyo Suda1, Motonari Uesugi1,2,3
1Institute for Chemical Research, Uji, Kyoto 611-0011, Japan. imiki@scl.kyoto-u.ac.jp.
Abstract:
Xanthine derivatives were identified as inhibitors of the N6-methyladenosine (m6A) demethylase activity of fat-mass-and-obesity-associated protein (FTO) by activity-based high-throughput screening using the m6A-sensitive ribonuclease MazF. Pentoxifylline exhibited L-ascorbic acid concentration-dependent inhibitory activity against FTO, an unprecedented mode of inhibition, indicating that L-ascorbic acid is a promising key for designing FTO-specific inhibitors.
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