LX2761 Acts Locally in GI Tract to Inhibit Sodium Glucose Transporter 1
Data Published in Oral Presentation at the American Diabetes Association Meeting
THE WOODLANDS, TX, USA I June 24, 2013 I Lexicon Pharmaceuticals, Inc. (LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, presented the first publication of data on LX2761 at the 73rd Scientific Sessions of the American Diabetes Association (ADA) in Chicago, on June 23, 2013.
David Powell, M.D., Lexicon’s senior vice president of metabolism research, delivered an oral presentation titled “LX2761, an SGLT1 Inhibitor Restricted to the Intestine, Improves Glycemic Control in Mice.” Dr. Powell’s presentation described the effects of LX2761 treatment on blood sugar control in mice with diabetes.
“LX2761 was designed to act locally in the gastrointestinal tract to reduce glucose absorption by inhibiting SGLT1 without any significant inhibition of SGLT2 in the kidney,” said Alan Main, Ph.D., Lexicon’s executive vice president of pharmaceutical research. “This was accomplished through a dedicated medicinal chemistry effort to identify molecules with limited systemic exposure that showed efficacy in animal models of diabetes.”
Consistent with design goals for an SGLT1 inhibitor without systemic exposure, LX2761 resulted in no urinary glucose excretion in mice while showing delayed intestinal glucose absorption and increased postprandial GLP-1 levels in mice, both alone and synergistically with the DPP-4 inhibitor sitagliptin. Notably, blood glucose excursions after an oral glucose challenge were still decreased 15 hours after oral LX2761 administration. Finally, LX2761 improved glycemic control in STZ-diabetic mice and in the KKAy mouse model of type 2 diabetes, as measured by reductions in hemoglobin A1c and oral glucose tolerance test results.
“We hope LX2761 may one day treat a large population of patients with diabetes, and potentially prediabetes, that may wish to avoid the urinary glucose excretion associated with SGLT2 inhibition in the kidney,” said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer. “In addition, the synergy demonstrated with a DPP-4 inhibitor provides the mechanistic rationale to consider future combination therapies.”
All presentations will be available for download from Lexicon’s corporate website www.lexpharma.com.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has multiple programs in clinical development for diabetes, irritable bowel syndrome, carcinoid syndrome and other indications, all of which were discovered by Lexicon‘s research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit www.lexpharma.com.
SOURCE: Lexicon
Post Views: 123
LX2761 Acts Locally in GI Tract to Inhibit Sodium Glucose Transporter 1
Data Published in Oral Presentation at the American Diabetes Association Meeting
THE WOODLANDS, TX, USA I June 24, 2013 I Lexicon Pharmaceuticals, Inc. (LXRX), a biopharmaceutical company focused on discovering breakthrough treatments for human disease, presented the first publication of data on LX2761 at the 73rd Scientific Sessions of the American Diabetes Association (ADA) in Chicago, on June 23, 2013.
David Powell, M.D., Lexicon’s senior vice president of metabolism research, delivered an oral presentation titled “LX2761, an SGLT1 Inhibitor Restricted to the Intestine, Improves Glycemic Control in Mice.” Dr. Powell’s presentation described the effects of LX2761 treatment on blood sugar control in mice with diabetes.
“LX2761 was designed to act locally in the gastrointestinal tract to reduce glucose absorption by inhibiting SGLT1 without any significant inhibition of SGLT2 in the kidney,” said Alan Main, Ph.D., Lexicon’s executive vice president of pharmaceutical research. “This was accomplished through a dedicated medicinal chemistry effort to identify molecules with limited systemic exposure that showed efficacy in animal models of diabetes.”
Consistent with design goals for an SGLT1 inhibitor without systemic exposure, LX2761 resulted in no urinary glucose excretion in mice while showing delayed intestinal glucose absorption and increased postprandial GLP-1 levels in mice, both alone and synergistically with the DPP-4 inhibitor sitagliptin. Notably, blood glucose excursions after an oral glucose challenge were still decreased 15 hours after oral LX2761 administration. Finally, LX2761 improved glycemic control in STZ-diabetic mice and in the KKAy mouse model of type 2 diabetes, as measured by reductions in hemoglobin A1c and oral glucose tolerance test results.
“We hope LX2761 may one day treat a large population of patients with diabetes, and potentially prediabetes, that may wish to avoid the urinary glucose excretion associated with SGLT2 inhibition in the kidney,” said Brian Zambrowicz, Ph.D., executive vice president and chief scientific officer. “In addition, the synergy demonstrated with a DPP-4 inhibitor provides the mechanistic rationale to consider future combination therapies.”
All presentations will be available for download from Lexicon’s corporate website www.lexpharma.com.
About Lexicon
Lexicon is a biopharmaceutical company focused on discovering breakthrough treatments for human disease. Lexicon currently has multiple programs in clinical development for diabetes, irritable bowel syndrome, carcinoid syndrome and other indications, all of which were discovered by Lexicon‘s research team. Lexicon has used its proprietary gene knockout technology to identify more than 100 promising drug targets. Lexicon has focused drug discovery efforts on these biologically-validated targets to create its extensive pipeline of clinical and preclinical programs. For additional information about Lexicon and its programs, please visit www.lexpharma.com.
SOURCE: Lexicon
Post Views: 123
