High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate.

Article Details

Citation

Copy to clipboard

Zolli-Juran M, Cechetto JD, Hartlen R, Daigle DM, Brown ED

High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate.

Bioorg Med Chem Lett. 2003 Aug 4;13(15):2493-6.

PubMed ID

12852950 [ View in PubMed

]

Abstract

This communication describes the high-throughput screen of a diverse library of 50,000 small molecules against Escherichia coli dihydrofolate reductase to detect inhibitors. Sixty-two compounds were identified as having significant inhibitory activity against the enzyme. Secondary screening of these revealed twelve molecules that were competitive with dihydrofolate, nine of which have not been previously characterized as inhibitors of dihydrofolate reductase. These novel molecules ranged in potency (K(i)) from 26 nM to 11 microM and may represent fresh starting points for new small molecule therapeutics directed against dihydrofolate reductase.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Trimethoprim	Dihydrofolate reductase	IC 50 (nM)	18	N/A	N/A	Details
Trimethoprim	Dihydrofolate reductase	IC 50 (nM)	37	N/A	N/A	Details
Trimethoprim	Dihydrofolate reductase	Ki (nM)	3.8	N/A	N/A	Details