Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6-bisphosphatase with a distinct binding mode

Thomas W von Geldern; Chunqiu Lai; Rebecca J Gum; Melissa Daly; Chaohong Sun; Elizabeth H Fry; Celerino Abad-Zapatero

doi:10.1016/j.bmcl.2006.01.015

Benzoxazole benzenesulfonamides are novel allosteric inhibitors of fructose-1,6-bisphosphatase with a distinct binding mode

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1811-5. doi: 10.1016/j.bmcl.2006.01.015. Epub 2006 Jan 25.

Authors

Thomas W von Geldern¹, Chunqiu Lai, Rebecca J Gum, Melissa Daly, Chaohong Sun, Elizabeth H Fry, Celerino Abad-Zapatero

Affiliation

¹ Metabolic Disease Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA. [email protected]

PMID: 16442285
DOI: 10.1016/j.bmcl.2006.01.015

Abstract

We have identified benzoxazole benzenesulfonamide 1 as a novel allosteric inhibitor of fructose-1,6-bisphosphatase (FBPase-1). X-ray crystallographic and biological studies of 1 indicate a distinct binding mode that recapitulates features of several previously reported FBPase-1 inhibitor classes.

MeSH terms

Allosteric Regulation
Benzoxazoles / chemistry*
Crystallography, X-Ray
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / metabolism
Enzyme Inhibitors / pharmacology*
Fructose-Bisphosphatase / antagonists & inhibitors*
Fructose-Bisphosphatase / metabolism
Models, Molecular
Protein Binding
Sulfonamides / chemistry
Sulfonamides / metabolism
Sulfonamides / pharmacology*

Substances

Benzoxazoles
Enzyme Inhibitors
Sulfonamides
Fructose-Bisphosphatase