Table 3: Activities of Confirmed Hits from Chemical Library Screen of Recombinant Human GAPDHS

No. GST-GAPDHS His-GAPDHS IC50 (µM)f
% Inhibition in HTS IC50 (µM)a Hill Slope Valueb LEc (kcal mol-1 non-H atom-1) BEId
1 70.1% 10.7 1.7 0.30 17 13
2 102.5% 6.5 1.1 0.47 24 11
3 90.3% 1.8 1.1 0.53 28 3
4 64.2% 16.8 1.0 0.55 28 30
5 56.0% 8.3 1.4 0.32 16 10
6 103.4% 11.9 1.0 0.27 14 12
7 45.9% 20.8 0.9 0.21 11 22
8 103.5% 36.1 1.1 0.38 20 44
9 33.8% 42.5 1.8 0.40 18 26
10 51.3% 45% inhibition at 80 µM 0.6 N/Ae N/A ND
11 101.1% 11.0 1.4 0.36 18 13
12 86.9% 30% inhibition at 80 µM N/A N/A N/A ND
13 52.6% 30% inhibition at 80 µM N/A N/A N/A ND
14 102.0% 30% inhibition at 80 µM N/A N/A N/A ND

a For IC50 determinations, serial dilutions of compounds were tested starting at a high concentration of 80 µM versus the E. coli expressed GST-GAPDHS. If 50% inhibition was not achieved at top dose, value is shown as % inhibition at 80 µM. IC50 values are the average for at least three independent determinations.
b IC50 and Hill slope values determined by XLfit software (ID Business Solutions).
c LE: ligand efficiency (Δg=ΔG Nnon-H atoms-1), a measure of the binding energy of the ligand per non-hydrogen atom [30].
d BEI: binding efficiency index (BEI=-logIC50 MW-1) a measure of the binding affinity of the ligand per ligand molecular weight [29].
e N/A not applicable, as a dose response curve was not generated.
f IC50 determinations from dose response against the baculovirus expressed his-GAPDHS [22]. Values determined by XLfit software (ID Business Solutions). ND, not determined.