Fig. 4: PAD-PF2 and GSK147 synergistically inhibit PAD4.

The method of Loewe³² was used to assess synergy between PAD-PF2 and GSK147 towards inhibition of PAD4. Serial dilutions of the inhibitors (0–3.6 μM) were tested in all combinations (two-by-two matrix) under the PAD4 GDH-coupled assay condition with 1.5 mM CaCl₂. Plotted are the normalized doses of the two compounds that were observed to produce half-maximal activity. For circles, x = [GSK147]/GSK147 IC₅₀ in the absence of PAD-PF2, y = PAD-PF2 IC₅₀/PAD-PF2 IC₅₀ in the absence of GSK147. For squares, x = GSK147 IC₅₀/GSK147 IC₅₀ in the absence of PAD-PF2, y = [PAD-PF2]/PAD-PF2 IC₅₀ in the absence of GSK147. Isobole represented by the dotted line. Source data are provided as a Source Data file.