title: Novel inhibitors of the high-affinity L-proline transporter as potential therapeutic agents for the treatment of cognitive disorders.
abstract: The incidence of cognitive disorders such as Alzheimer's disease continues to increase unabated. While cures for such diseases have eluded investigators, progress is being made on alleviating certain symptoms of these diseases. Mouse knockouts of the proline transporter (PROT), a high affinity Na(+)/Cl(-)-dependent transporter, indicated its potential as a novel therapeutic target for cognition improvement. Herein we report our investigation into a novel class of PROT inhibitors.
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States. Electronic address: ggzipp@yahoo.com.
authors.forename: G Greg
authors.initials: GG
authors.lastname: Zipp
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Barbosa
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Green
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Terranova
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fink
authors.affiliation: Department of Pharmaceutical Discovery, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Xuan-Chuan
authors.initials: XC
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Discovery, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Amr
authors.initials: A
authors.lastname: Nouraldeen
authors.affiliation: Department of Pharmaceutical Discovery, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Department of Neurology, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Katerina
authors.initials: K
authors.lastname: Savelieva
authors.affiliation: Department of Neurology, Lexicon Pharmaceuticals, 8800 Technology Forest Place, The Woodlands, TX 77381, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Lanthorn
authors.affiliation: Department of Medicinal Chemistry, Lexicon Pharmaceuticals, 350 Carter Rd., Princeton, NJ 08540, United States.
authors.forename: S
authors.initials: S
authors.lastname: David Kimball
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D054852:Small Molecule Libraries; C041832:proline transport protein
keywords: Acyl piperazine; Alzheimer’s disease; Dimentia; Inhibitor; Proline transporter