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Description: TCS-OX2-29 HCl, discovered from high throughput screening (HTS), is a potent and selective OX2 receptor antagonist with IC50 of 40 nM. It displays > 250-fold selectivity for OX2 over OX1. Orexin receptor antagonism represents a novel approach for the treatment of insomnia that directly targets sleep/wake regulation. Several such compounds have entered into clinical development, including the dual orexin receptor antagonists, suvorexant and almorexant. TCS-OX2-29 shows selectivity for ion channels, and transporters (< 30% inhibition at 10 uM), which includes G-protein coupled receptors associated with food intake including galanin and neuripeptide Y. TCS-OX2-29 Inhibits orexin A induced IP3 accumulation and ERK1/2 phosphorylation in CHO cells transfected with the OX2 receptor.
References: Bioorg Med Chem Lett. 2003 Dec 15; 13(24):4497-9.Br J Pharmacol. 2014 Jan; 171(2):351-63.
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