LY2365109 is a potent and selective GlyT1 inhibitors with IC50 value of 15.8 nM.target: GlyT1[1]IC 50: 15.8 nM [1]In vivo: The reference for LY2365109 is 0.3 or 30 mg/kg by PO. LY2365109 appeared slightly more potent than ALX5407 over the dose-range tested on CSF levels of glycine in the ratLY2365109 can act to potentiate NMDA function in the PFC but also mediate sustained inhibition of GlyT1 transporters in caudal areas of the brain.[1] LY2365109 increased seizure thresholds in mice. Importantly, chronic seizures in the mouse model of TLE were robustly suppressed by systemic administration of the GlyT1 inhibitor LY2365109. [2]
References:
[1]. Perry KW et al. Neurochemical and behavioral profiling of the selective GlyT1 inhibitors ALX5407 and LY2365109 indicate a preferential action in caudal vs. cortical brain areas. Neuropharmacology. 2008 Oct;55(5):743-54.
[2]. Shen HY et al. Glycine transporter 1 is a target for the treatment of epilepsy. Neuropharmacology. 2015 Dec;99:554-65.