Percent inhibition

Cheng, Y. C., andPrasoff, W. H. (1973). Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 percent inhibition (150) of an enzymatic reaction. Biochem. Pharmacol. 22 3099—3108. 

Effect of PG inhibitor concentration on PG activity Various amounts of inhibitor were added in the assay mixture and the degree of inhibition of polygalacturonase activity was measured which showed a linear relationship between inhibitor concentration and percent inhibition... 

NOTE [ H]MDA binding assays were performed in 50 mM Tris-HCl (ph 7.1) containiag 0.27 M sucrose and 2.0 nM [ H]MDA as described in the text. Results are expressed as percent inhibition of specific [ HJMDA incorporation in the absence of inhibitors. Boiled tissue blanks were performed at each concentration of drug. 

Fig. 9 Inhibition of dofetilide binding (percent inhibition 10 pM) vs clogD. Series A (black stars) and series B open circles) are structurally distinct...

Sub-type inhibition of the 5a-reductase enzyme Percent of inhibition of serum dihydrotestosterone level Percent of patients with reduction in serum dihyrotestosterone Time to peak onset of reduction in serum dihydrotestosterone level Percent inhibition of intraprostatic d i hy d rotestosterone Half-life... 

Figure 14.8 (A) Screening of a glycopeptide library using a fluorescent-labeled lectin and ligands bound to PEGA beads. The acbve compounds are analysed by mass spectrometry. (B) FITC-labeled lectin binding to resin bound mannose could be inhibited by soluble glycopeptides obtained from library screen. Percent inhibition was quantified by recording of lectin fluorescence. Only every second well of the microtiter plate was used and nonfluorescent beads indicated good inhibitors.44...

Figure2.5 Biological fingerprint forclozapine showingthe results for assays with a percent inhibition >90% at 10 pM (upper line, red). The IC50S are shown as color coded on the lower line (red < 100 nM, orange < 1 jj,M, yellow < 5pM).

Figure 5. Inhibitory effect of NO on Fe -induced lipid peroxidation. Shown is the decreased generation of an oxidative marker (thiobarbituric acid reactive substances, TBARS) as a result of 0.9 iM NO. HL-60 cells (5 x loVral) were placed in an O2 monitor and at the designated time points, butylated hydroxytoluene was added and samples were quick frozen for determination of TBARS. The values represent the mean and standard error of 3-5 independent determinations. Also shown for comparison is the residual concentration of O2 after exposure to the the same conditions. This shows a decrease in utilization of O2 in the presence of NO. We conclude that NO reduces TBARS, and the percent inhibition is similar to the poeent inhibition of O2 consumption. (Modified from our data in Kelley, E.E., Wagner, B.A., Buettner, G.R., and Bums, C.P., 1999, Arch. Biochem. Biophys. 370 97-104).

Fig. 6.1 Activity histogram (left Y axis) and cumulative frequency curve (right Y axis) versus binned percent inhibition (X axis) for a recent primary HTS run at Wyeth. Note the sudden spike in the cumulative frequency curve for compounds with >100% inhibition, corresponding to the 0.2% most active compounds.

Fig. 6.2 Plot of percent inhibition in the primary HTS assay versus IC50 ( J.M) in a secondary in vitro assay for 118 compounds of interest identified from a recent Wyeth HTS. Note the relatively flat correlation such that compounds with low percent inhibition (e.g., 50%) have IC50S, on average, only one order of magnitude less than compounds with maximal ( 100%) inhibition.

Fig. 6.7 Visualization of HTS data using Spotfire decision site [48]. Shown are a table of data (top left), a bar chart (top right, number of compounds screened from each plate), 3-D scatterplot (bottom left, percent inhibition in the primary assay versus percent inhibition in the confirmation assay versus percent purity), and a plate map (bottom right, well versus Column arranged by plate number). In the 3-D scatterplot and the plate map, the points are colored by plate number and sized by percent inhibition in the primary assay.

The confirmation rates for the selected set at different primary and confirmation percent inhibition thresholds appear in Table 6.2. Also shown are confirmation rates for those subsets of the selected that appear in the Top X selection either before or after filtering, which is the union of the selected set and the respective Top 4000 selections. The confirmation rate holds remarkably steady for all three sets at the four different thresholds for the primary inhibition examined if the threshold used to define confirmed actives is kept constant at 30%. If the confirmation threshold is instead increased along with the primary threshold, the confirmation rate drops for all three sets, which might be considered counterintuitive. However, this can be explained by the twin influences of edge effects (Section 6.1.5) and the enrichment of false positives at higher activities. This behavior has been reported previously by Fay and Ullmann [31] for both real... 

Tab. 6.2 Confirmation rates for three sets of compounds at different thresholds for primary and confirmation percent inhibition...

After removing duplicates, 4905 actives remained with percent inhibition >40%. Of these, 992 compounds with 175 > MW > 600, clogP > 6, donors > 5, acceptors > 10, rotatable bonds > 10 or TPSA > 140 were flagged and subject to visual assessment in Spotfire by a medicinal chemist. Approximately half of these were retained, leaving 4458 actives from this set for confirmation assays. 

The 5 k actives with percent inhibition of 25 to 40% and that feU into clusters of less than five compounds were treated separately using BCUT diversity analysis, as described in Section 6.2.5. A cell-based selection biased by primary activity from six bins per each of six axes yielded 1258 compounds. The combined selection from filtering, clustering, and diversity totaled 6986 compounds representing 3337 ring scaffolds and was submitted for confirmation assays. Note that the full set of 16 k filtered actives contained 9254 ring hashcodes, so the selected set covers 36.1% of the represented scaffolds. Because of the presence of duplicate samples in the corporate screening collection, 7275 samples were pulled and assayed. 

The percent inhibition was calculated according to the equation in Table II. As shown in Table II, the results indicated that when compared to the polyacrylic acid, copolymers of acrylic acid and N-(hydroxyalkyl)-acrylamide were quite effective in inhibiting calcium phosphate formation at the normal use dosage of 10 to 20 ppm. Among the three copolymers tested, acrylic acid/... 

Structure-activity correlations are usually quantitated on the basis of biological data obtained in vitro. For example, the values for 50 percent inhibition (PI50) Hill... 

When the duration of exposure to GT-4 was limited to 10 minutes and the percent inhibition for an agonist concentration equivalent to the 50% control response was measured at 90 minutes as a function of toxin concentration, a linear response was obtained (Figure 5). Figure 5 shows that the exposure of the preparation to 2.8 ng/ml, 7.0 ng/ml and 70 ng/ml for 10 minutes resulted in inhibitions of 30, 36, and 66% of the contractile response from control levels, respectively. In addition, exposure of the preparation to 2.8, 7.0 and 70 ng/ml for 15 minutes resulted in 45, 55, and 98% inhibition of the contractile response, respectively. We can express the effects of GT-3 by stating both the dose and time to achieve a 50% inhibition from the control or a DCI50 value. 

Figure 5. Percent inhibition as a function of time toxin is applied and concentration.

Figure 6. Effect of high and low calcium on the percent inhibition at a constant concentration of toxin.

Slope break point of percent inhibition data. 

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