3-(2-carboxyethyl)-4,6-dichloro-1H-indole-2-carboxylic acid: an allosteric inhibitor of fructose-1,6-bisphosphatase at the AMP site.
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.
Wright
Stephen W
SW
Pfizer Central Research, Eastern Point Road, Box 8220-3141, Groton, CT 06340, USA. stephen_w_wright@groton.pfizer.com
Carlo
Anthony A
AA
Danley
Dennis E
DE
Hageman
David L
DL
Karam
George A
GA
Mansour
Mahmoud N
MN
McClure
Lester D
LD
Pandit
Jayvardhan
J
Schulte
Gayle K
GK
Treadway
Judith L
JL
Wang
Ing-Kae
IK
Bauer
Paul H
PH
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
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