title: 3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.
abstract: 3-(2-Carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid (MDL-29951), an antagonist of the glycine site of the NMDA receptor, has been found to be an allosteric inhibitor of the enzyme fructose 1,6-bisphosphatase. The compound binds at the AMP regulatory site by X-ray crystallography. This represents a new approach to inhibition of fructose 1,6-bisphosphatase and serves as a lead for further drug design.
authors.affiliation: Pfizer Central Research, Eastern Point Road, Box 8220-3141, Groton, CT 06340, USA. stephen_w_wright@groton.pfizer.com
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wright
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Carlo
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Danley
authors.forename: David L
authors.initials: DL
authors.lastname: Hageman
authors.forename: George A
authors.initials: GA
authors.lastname: Karam
authors.forename: Mahmoud N
authors.initials: MN
authors.lastname: Mansour
authors.forename: Lester D
authors.initials: LD
authors.lastname: McClure
authors.forename: Jayvardhan
authors.initials: J
authors.lastname: Pandit
authors.forename: Gayle K
authors.initials: GK
authors.lastname: Schulte
authors.forename: Judith L
authors.initials: JL
authors.lastname: Treadway
authors.forename: Ing-Kae
authors.initials: IK
authors.lastname: Wang
authors.forename: Paul H
authors.initials: PH
authors.lastname: Bauer
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D000495:Allosteric Site; D000818:Animals; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D008958:Models, Molecular; D011422:Propionates / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: C000588735:2-carboxy-4,6-dichloro-(1H)-indole-3-propanoic acid; D004791:Enzyme Inhibitors; D007211:Indoles; D011422:Propionates; D011994:Recombinant Proteins; D000249:Adenosine Monophosphate; D006597:Fructose-Bisphosphatase