Fig. 1
From: Screening of the FDA-approved drug library identifies CCL17 inhibitors that block arthritic pain
CCL17-inhibiting candidates from the screening of the FDA-approved drug library. (A) Summary of drug screening depicting that among the 1508 FDA-approved drugs, 228 drugs inhibited GM-CSF-induced CCL17 expression by 75%. Following MTT viability assay, 146 of the CCL17-inhibintg drugs showed no toxic effects on human monocytes. These drugs were further analyzed for their effects on CCL22 expression using the same supernatants. Among the 146 drugs, only 21 drugs had no inhibitory effects on basal CCL22 expression in human monocytes. These 21 drugs were further evaluated for their inhibitory effects using monocytes from multiple donors. Among these 21 drugs, 17 drugs consistently inhibited GM-CSF-induced CCL17 expression and 14 of them did not inhibit CCL22 expression. (B,C) Human monocytes were pre-treated with either PBS or one of the CCL17-inhibiting drugs (10 µM), identified by the high-throughput screening, for 30 min before being treated with GM-CSF (20 ng/mL) for 16 h. Monocyte culture supernatants were subjected to (B) CCL17 and (C) CCL22 ELISA. Data are graphed as scatter plots with bars indicating mean ± SEM. P values were obtained using one-way ANOVA with Tukey post-test (n = 4–5), where * < 0.05, **< 0.01, *** <0.001. ND, not detected, and NS, not significant. The complete list of FDA-approved drugs and their effects on CCL17 (and CCL22) are provided in Supplementary Table 1.
