Results of NCDS's HTS of 160,000 compounds against the <i>B. malayi</i> iPGAM.

<p>The distribution of compounds is shown as a function of percent inhibition of the enzyme.</p

Robustness of the HTS assays performed at Genzyme (top) and NCDS (bottom).

<p>TOP: scattergram of percent inhibition data from all plates in the Genzyme HTS. Green: 100% inhibition control; red: 50% inhibition control; black: 0% inhibition control; blue: data for test compounds screened at 10 µM. BOTTOM: scattergram of NCDS data representing uninhibited iPGAM (2% DMSO, shown in red) and inhibited iPGAM (200 µM tannic acid, shown in black). 1120 wells for each condition, spread over seventy 384-well plates, are shown. Dashed lines indicate means ±3× standard deviation (SD).</p

Dose-response curve of the confirmed hit NCDS-1. NCDS-1 and control inhibitor tannic acid were tested at concentrations from 0.78 µM to 400 µM.

<p>Note that tannic acid may inhibit iPGAM via nonspecific aggregation <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002628#pntd.0002628-Pohjala1" target="_blank">[40]</a>; this would render it unsuitable as a chemical probe, but does not prevent its use as a control inhibitor for comparison of inhibited and uninhibited samples. Nonlinear regression and IC₅₀ value were analyzed with GraphPad Prism software (GraphPad, San Diego, CA, USA). Data are expressed as means ± SEM of at least 3 independent experiments.</p

Novel inhibitors of <i>B. malayi</i> iPGAM.

<p>N.D. = Not determined.</p

A summary of the screening workflow at the two HTS sites, along with the number of compounds passing through each step.

<p>See <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0002628#s2" target="_blank">Methods</a> for details.</p