Purity: > 98%
LX1606 is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor with potential antiserotonergic activity.
Target: Tryptophan hydroxylase
in vivo: LX1606 (LX 1606, LX-1606) is useful for Neurological Diseas . LX1606 were given orally to mice. LX1606 reduced 5-HT significantly in the gut and blood but not in the brain. oral LX1032 reduced the severity of TNBS-induced colitis; the expression of 24% of 84 genes encoding inflammation-related cytokines and chemokines was lowered at least fourfold and the reduced expression of 17% was statistically significant . Treatment with LX1606 showed a strong positive effect in ameliorating TNBS-induced IBD in mice as assessed by various parameters of disease development. These preclinical data demonstrate that inhibition of TPH activity by LX1606 may provide a new approach for the treatment of IBD and its serotonin-mediated symptoms.
1:Am J Physiol Gastrointest Liver Physiol. 2015 Sep 15;309(6):G455-65. doi: 10.1152/ajpgi.00299.2014. Epub 2015 Jul 23. Blocking peripheral serotonin synthesis by telotristat etiprate (LX1032/LX1606) reduces severity of both chemical- and infection-induced intestinal inflammation.Kim JJ,Wang H,Terc JD,Zambrowicz B,Yang QM,Khan WI, PMID: 26206858 DOI: 10.1152/ajpgi.00299.2014
Abstract: Mucosal inflammation is accompanied by an alteration in 5-HT. Intestinal 5-HT synthesis is catalyzed by tryptophan hydroxylase 1 (Tph1) and we have shown that mice deficient in this rate-limiting enzyme have reduced severity of intestinal inflammation in models of chemical-induced experimental colitis. Here, we investigated the effect of blocking peripheral 5-HT synthesis in generation of intestinal inflammation by a using peripheral Tph inhibitor, telotristat etiprate (LX1606), in models of intestinal inflammation. LX1606 was given orally either prophylactically or therapeutically to mice with dextran sulfate sodium (DSS)-induced colitis or with infection with Trichuris muris. Severity of intestinal inflammation was measured by assessment of disease activity scores, histological damage, and MPO and inflammatory cytokine levels. LX1606 significantly reduced intestinal 5-HT levels and delayed onset and severity of DSS-induced acute and chronic colitis. This was associated with decreased MPO and proinflammatory cytokine levels compared with vehicle-treated controls. In the infection-induced inflammation model, treatment with LX1606 enhanced worm expulsion as well as increased IL-10 production and goblet cell numbers. LX1606-treated mice had significantly lower MPO and IL-1β levels compared with controls postinfection. Our results demonstrate that peripheral 5-HT plays an important role in intestinal inflammation and in the generation of immune responses. Pharmacological reduction of peripheral 5-HT may serve as a potential strategy for modulating various intestinal inflammatory disorders. Copyright © 2015 the American Physiological Society.