- Zheng G, Cox T, Tribbey L, Wang GZ, Iacoban P, Booher ME, Gabriel GJ, Zhou L, Bae N, Rowles J. (2014) Synthesis of a FTO Inhibitor with Anticonvulsant Activity. ACS Chem Neurosci 5(8), 658-665.
We describe the rationale for and the synthesis of a new class of compounds utilizing a modular approach that are designed to mimic ascorbic acid and to inhibit 2-oxoglutarate-dependent hydroxylases. Preliminary characterization of one of these compounds indicates in vivo anticonvulsant activity (6Hz mouse model) at non-toxic doses, inhibition of the 2-oxoglutarate-dependent hydroxylase FTO, and expected increase in cellular N6-methyladenosine. This compound is also able to modulate various microRNA, an interesting result in light of the recent view that modulation of microRNAs may be useful for the treatment of CNS disease.