LX1606

• CAT Number: I000202
• CAS Number: 1033805-22-9
• Molecular Formula: C27H26ClF3N6O3
• Molecular Weight: 574.98
• Purity: 98%
• Target: Tryptophan hydroxylase
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IUPAC Name: ethyl (2S)-2-amino-3-[4-[2-amino-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl]phenyl]propanoate
• InChI: InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1
• InChIKey: MDSQOJYHHZBZKA-GBXCKJPGSA-N
• SMILES: CCOC(=O)C(CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)OC(C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)N

LX1606（Cat No.:I000202） is a small-molecule compound that is administered orally and functions as a tryptophan hydroxylase (TPH) inhibitor. TPH is an enzyme involved in the synthesis of serotonin, a neurotransmitter implicated in various physiological and neurological processes. By inhibiting TPH, LX1606 can reduce serotonin levels, leading to potential antiserotonergic effects. LX1606 is being investigated for its therapeutic potential in conditions associated with excessive serotonin activity, such as carcinoid syndrome and other neuroendocrine tumors.

Reference

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.