Metabolism
Obesity, Diabetes, Osteoporosis, HyperlipidemiaMetabolic disorders include the serious and growing problems of obesity and diabetes and the complications they cause. According to the World Health Organization, more than 300 million adults worldwide are now considered obese. Obesity is also a contributing factor to over 30 diseases, including diabetes, heart disease and stroke. According to the International Diabetes Federation, more than 194 million people worldwide suffer from diabetes. Current pharmaceutical treatments for obesity have shown only limited effectiveness and have exhibited unfavorable side effects. Current treatments for diabetes also have significant limitations.
LX1031 for Irritable Bowel Syndrome
LX1031 is an orally-delivered small molecule compound for the potential treatment of irritable bowel syndrome and other gastrointestinal disorders. We initiated a Phase 1b clinical trial for LX1031 in April 2007. The Phase 1b trial is a randomized, double-blind, placebo-controlled, multiple-ascending dose study in which LX1031 is being studied in approximately 40 normal healthy volunteers. We have designed LX1031 to act locally in the gastrointestinal tract by reducing the serotonin available for receptor activation, but without affecting serotonin levels in the brain or its central nervous system functions. We intend to use serotonin as a biomarker by which to evaluate the activity of LX1031 in clinical trials. LX1031 was internally generated by our medicinal chemists, and its target was identified as part of our Genome5000 program as a key control point for the regulation of peripheral serotonin levels. We conducted a Phase 1a clinical trial for LX1031 in January 2007, during which LX1031 was well tolerated at all dose levels studied. In preclinical studies, LX1031 demonstrated a dose-dependent reduction of serotonin levels in the gastrointestinal tract of multiple species with no observed adverse effects across a broad range of medically-relevant parameters.
Related Publications
Brown PM, Jackson JI, Frazier KS, Turner CA, Shi ZC, Liu Q (2007). From Mouse Knockout to Investigational Drug: LX1031, A Novel Potential Treatment for Irritable Bowel Syndrome. 2007 Annual Scientific Meeting of the American College of Gastroenterology.
Poster
8.73 MBLX1032 for Gastrointestinal Disorders
LX1032 is an orally-delivered small molecule compound that we are developing for the potential treatment of gastrointestinal disorders. We have commenced formal preclinical development for LX1032 in preparation for the expected filing of an IND application in 2007. LX1032 modulates the same target as LX1031, but the two compounds are chemically distinct. LX1032 was internally generated by our medicinal chemists and was specifically designed to achieve systemic exposure. LX1032 may provide an additional therapeutic approach for functional and other gastrointestinal disorders that require systemic regulation of serotonin levels.