Background:

Tryptophan hydroxylase (TPH) is a key enzyme in the synthesis of serotonin. Serotonin plays important physiological roles both peripherally and centrally. LX-1031 is a heterocyclic substituted phenylalanine analog, an oral small molecule tryptophan hydroxylase (TPH) inhibitor that reduces synthesis of serotonin (5-HT) peripherally and is being developed for conditions characterized by excess 5-HT expression such as diarrhea-predominant irritable bowel syndrome (IBS-D) and, possibly, carcinoid diarrhea.

In vitro: LX-1031 inhibits TPH1 at its concentration of 10-8–10-7 mol L-1 range [1].

In vivo: With oral administration of LX-1031 in mice, the 5-HT reductions in the jejunum relative to control were