生物活性

• 描述The dysfunction of the peripheral serotonin (5-hydroxytryptamine, 5-HT) system is involved in many diseases, such as carcinoid syndrome, fibrotic disease, atherosclerosis, and pulmonary arterial hypertension. Tryptophan hydroxylase 1 (TPH1) is an aromatic amino acid hydroxylase essential for the biosynthesis of peripheral 5-HT. Telotristat etiprate is the ester prodrug of a potent TPH1 inhibitor, LX-1033, with an IC50 value of 16nM^[2]. Telotristat (also known as LP778902) is the active moiety of telotristat etiprate. In C57BL/6 mice, telotristat (~100 mg/kg) supplementation significantly reduced maternal serum serotonin concentration compared with the control dams on day 1 and day 21 of lactation, but did not change serum serotonin level in their pups. Maternal supplementation with telotristat did not significantly alter the ratio of maternal femoral trabecular bone volume to tissue volume. Pups of the dams treated with telotristat showed a reduced ratio of bone volume to tissue volume on the day of weaning, fewer and thinner trabeculae, and increased trabecular spacing compared with control pups. Pups born to telotristat-supplemented dams also had reduced total serum calcium on day 21 of lactation^[3].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00853047	Carcinoid Syndrome	Phase 2	Completed	-	United States, Arkansas ... more >> Hematology Oncology Services of Arkansas Little Rock, Arkansas, United States, 72205 United States, California UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115 United States, Indiana St. Francis Medical Group Oncology and Hematology Specialists Indianapolis, Indiana, United States, 46237 United States, Iowa University of Iowa Iowa City, Iowa, United States, 52242 United States, Massachusetts Dana Farber Cancer Institute Boston, Massachusetts, United States, 02115 United States, Nebraska Nebraska Methodist Hospital Omaha, Nebraska, United States, 68114 United States, Texas UT M.D. Anderson Cancer Center Houston, Texas, United States, 77030 Texas Oncology - McAllen McAllen, Texas, United States, 78503 Texas Oncology - Weslaco Weslaco, Texas, United States, 78596 Collapse <<
  NCT01104415	Symptoms of Carcinoid Syndrome	Phase 2	Completed	-	Germany ... more >> Lexicon Investigational Site Bad Berka, Germany Lexicon Investigational Site Berlin, Germany Lexicon Investigational Site Halle, Germany Lexicon Investigational Site Lubeck, Germany Lexicon Investigational Site Marburg, Germany Lexicon Investigational Site Munich, Germany United Kingdom Lexicon Investigational Site Basingstoke, United Kingdom Lexicon Investigational Site Cambridge, United Kingdom Lexicon Investigational Site London, United Kingdom Lexicon Investigational Site Manchester, United Kingdom Collapse <<
  NCT01456052	Ulcerative Colitis	Phase 2	Completed	-	United States, Arkansas ... more >> Lexicon Investigational Site Little Rock, Arkansas, United States, 72205 United States, California Lexicon Investigational Site Anaheim, California, United States, 92801 Lexicon Investigational Site Santa Monica, California, United States, 90404 United States, New York Lexicon Investigational Site Great Neck, New York, United States, 11021 Lexicon Investigational Site New York, New York, United States, 10017 United States, Oklahoma Lexicon Investigational Site Tulsa, Oklahoma, United States, 74135 United States, Texas Lexicon Investigational Site Houston, Texas, United States, 77030 Lexicon Investigational Site San Antonio, Texas, United States, 78229 United States, Utah Lexicon Investigational Site Ogden, Utah, United States, 84405 Lexicon Investigational Site Sandy City, Utah, United States, 84094 United States, Washington Lexicon Investigational Site Seattle, Washington, United States, 98195 Lithuania Lexicon Investigational Site Kaunas, Lithuania, LT-50009 Lexicon Investigational Site Klaipeda, Lithuania, LT-92288 Lexicon Investigational Site Siauliai, Lithuania, LT-76231 Lexicon Investigational Site Vilnius, Lithuania, LT-03215 Lexicon Investigational Site Vilnius, Lithuania, LT-08661 Poland Lexicon Investigational Site Krakow, Poland, 31531 Lexicon Investigational Site Lodz, Poland, 90302 Lexicon Investigational Site Sopot, Poland, 81756 Lexicon Investigational Site Warszawa, Poland, 03580 Lexicon Investigational Site Wroclaw, Poland, 53025 Lexicon Investigational Site Wroclaw, Poland, 54144 Slovakia Lexicon Investigational Site Nitra, Slovakia, 94901 Lexicon Investigational Site Nove Mesto nad Vahom, Slovakia, 91501 Collapse <<

• 更多
• 参考文献

• [1] Margolis KG, Stevanovic K, et al. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut. 2014 Jun;63(6):928-37.

  [2] Goldberg DR, De Lombaert S, Aiello R, Bourassa P, Barucci N, Zhang Q, Paralkar V, Stein AJ, Valentine J, Zavadoski W. Discovery of acyl guanidine tryptophan hydroxylase-1 inhibitors. Bioorg Med Chem Lett. 2016 Jun 15;26(12):2855-2860.

  [3] Weaver SR, Fricke HP, Xie C, Aiello RJ, Charles JF, Hernandez LL. Peripartum dietary supplementation of a small-molecule inhibitor of tryptophan hydroxylase 1 compromises infant, but not maternal, bone. Am J Physiol Endocrinol Metab. 2018;315(6):E1133-E1142.