PLoS ONE 2009-01-01

A high-throughput approach for identification of novel general anesthetics.

Wendy A Lea, Jin Xi, Ajit Jadhav, Louis Lu, Christopher P Austin, Anton Simeonov, Roderic G Eckenhoff

文献索引：PLoS ONE 4(9) , e7150, (2009)

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摘要

Anesthetic development has been a largely empirical process. Recently, we described a GABAergic mimetic model system for anesthetic binding, based on apoferritin and an environment-sensitive fluorescent probe. Here, a competition assay based on 1-aminoanthracene and apoferritin has been taken to a high throughput screening level, and validated using the LOPAC(1280) library of drug-like compounds. A raw hit rate of approximately 15% was reduced through the use of computational filters to yield an overall hit rate of approximately 1%. These hits were validated using isothermal titration calorimetry. The success of this initial screen and computational triage provides feasibility to undergo a large scale campaign to discover novel general anesthetics.