With 25 uM protein, any inhibitor with a Kd of 12.5 uM or lower (half of 25 uM) will have the same IC50 (concentration giving 50% inhibition of ligand binding), 12.5 uM, assuming a binding stoichiometry of 1 and the ligand concentration is well below its Kd. A compound can not inhibit by more than 50% if there is not enough of it to occupy more than 50% of the binding sites. So you are correct in worrying that your assay will not be able to discriminate among potent compounds. The solution to this problem is to find a ligand with higher affinity so that you can lower the protein concentration, or identify a different assay format that uses a lower protein concentration.

two useful references:

1. Roehrl, M.H.A., J.Y. Wang, and G. Wagner, A general framework for

development and data analysis of competitive high-throughput screens for

small-molecule inhibitors of protein−protein interactions by fluorescence

polarization. Biochemistry, 2004. 43(51): pp. 16056-16066.

2. Huang, X., Fluorescence polarization competition assay: The range of

resolvable inhibitor potency is limited by the affinity of the fluorescent

ligand. J. Biomol. Screen., 2003. 8(1): pp. 34-38.