FIGURE 2.

Identification of activity-selective LRRK2 inhibitors. A, measurement of ADP formation with the addition of 5 μm of LRRK2 peptide substrate or without (Autophos). B and C, determination of ATP affinity for WT (B) and G2019S-LRRK2 protein (C) with respect to LRRK2 cis-autophosphorylation. D, IC₅₀ values were calculated from compounds that demonstrated measurable inhibition of either WT or G2019S-LRRK2 autophosphorylation activity. E, cis-autophosphorylation inhibition plotted against trans-peptide inhibition for the same set of compounds. A list of compound identities is given in supplemental Table 1. F and G, examples of commercially available compounds selective for inhibition of cis-autophosphorylation (F) or trans-peptide phosphorylation (G). The indicated values were derived from at least three independent assays, and data are mean ± S.D.