title: Discovery of LX2761, a Sodium-Dependent Glucose Cotransporter 1 (SGLT1) Inhibitor Restricted to the Intestinal Lumen, for the Treatment of Diabetes.
abstract: The increasing number of people afflicted with diabetes throughout the world is a major health issue. Inhibitors of the sodium-dependent glucose cotransporters (SGLT) have appeared as viable therapeutics to control blood glucose levels in diabetic patents. Herein we report the discovery of LX2761, a locally acting SGLT1 inhibitor that is highly potent in vitro and delays intestinal glucose absorption in vivo to improve glycemic control.
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals , 110 Allen Road, Basking Ridge, New Jersey 07920, United States.
authors.forename: Nicole C
authors.identifier: 0000-0002-6093-7175
authors.initials: NC
authors.lastname: Goodwin
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Ding
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals , 110 Allen Road, Basking Ridge, New Jersey 07920, United States.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Harrison
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals , 110 Allen Road, Basking Ridge, New Jersey 07920, United States.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Strobel
authors.forename: Angela L
authors.initials: AL
authors.lastname: Harris
authors.forename: Melinda
authors.initials: M
authors.lastname: Smith
authors.forename: Andrea Y
authors.initials: AY
authors.lastname: Thompson
authors.forename: Wendy
authors.initials: W
authors.lastname: Xiong
authors.forename: Faika
authors.initials: F
authors.lastname: Mseeh
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Bruce
authors.forename: Damaris
authors.initials: D
authors.lastname: Diaz
authors.forename: Suma
authors.initials: S
authors.lastname: Gopinathan
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Emily
authors.initials: E
authors.lastname: O'Neill
authors.forename: Mary
authors.initials: M
authors.lastname: Thiel
authors.forename: Alan G E
authors.initials: AG
authors.lastname: Wilson
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals , 110 Allen Road, Basking Ridge, New Jersey 07920, United States.
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Carson
authors.forename: David R
authors.initials: DR
authors.lastname: Powell
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals , 110 Allen Road, Basking Ridge, New Jersey 07920, United States.
authors.forename: David B
authors.initials: DB
authors.lastname: Rawlins
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D018345:Mice, Knockout; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013865:Thioglycosides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D007004:Hypoglycemic Agents; C000620658:LX2761; D010654:Phenylbutyrates; C495674:SLC5A1 protein, human; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D013865:Thioglycosides; D005947:Glucose