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A Unique Small Molecule Inhibitor of Enolase Clarifies Its Role in Fundamental Biological Processes
- Source :
- ACS Chemical Biology. 8:1271-1282
- Publication Year :
- 2013
- Publisher :
- American Chemical Society (ACS), 2013.
-
Abstract
- Enolase is a component of the glycolysis pathway and a "moonlighting" protein, with important roles in diverse cellular processes that are not related to its function in glycolysis. However, small molecule tools to probe enolase function have been restricted to crystallography or enzymology. In this study, we report the discovery of the small molecule "ENOblock", which is the first, nonsubstrate analogue that directly binds to enolase and inhibits its activity. ENOblock was isolated by small molecule screening in a cancer cell assay to detect cytotoxic agents that function in hypoxic conditions, which has previously been shown to induce drug resistance. Further analysis revealed that ENOblock can inhibit cancer cell metastasis in vivo. Moreover, an unexpected role for enolase in glucose homeostasis was revealed by in vivo analysis. Thus, ENOblock is the first reported enolase inhibitor that is suitable for biological assays. This new chemical tool may also be suitable for further study as a cancer and diabetes drug candidate.
- Subjects :
- Protein moonlighting
Alpha-enolase
Molecular Sequence Data
Enolase
Antineoplastic Agents
Biochemistry
Small Molecule Libraries
Cell Movement
In vivo
Cell Line, Tumor
Neoplasms
Drug Discovery
Animals
Humans
Glucose homeostasis
Neoplasm Invasiveness
Amino Acid Sequence
Enzyme Inhibitors
Zebrafish
Adipogenesis
biology
Triazines
Drug discovery
General Medicine
Small molecule
Cell biology
Glucose
Phosphopyruvate Hydratase
Benzamides
Cancer cell
biology.protein
Molecular Medicine
Foam Cells
Subjects
Details
- ISSN :
- 15548937 and 15548929
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- ACS Chemical Biology
- Accession number :
- edsair.doi.dedup.....1ab0162e6734e96a0f9c7c68827b03a9