Figure 7.
BAL-0028 and BAL-0598 inhibit NLRP3-AID mutants. (A–F) IL-1β release assays from LPS and nigericin-stimulated PBMCs pre-treated with MCC950 (200, 1,000 nM) or BAL-0028 (200, 1,000 nM). Data from (A) healthy controls or patients with NLRP3-AID mutations (B) T348M, (C) A352V, (D and E) A439V, and (F) Y570C. Graph symbols show average IL-1β values ± SEM from N = 3 (A) or N = 1 (B–F) independent experiments performed in biological triplicate. (G) Comparison of BAL-0028 and MCC950 (40–1,000 nM) in a cell death assay in U937 cells expressing NLRP3 or NLRP3-AID mutants (D303H, A352V, L353P, K565E, E567G, K568N, G569R, and Y570C) stimulated with LPS and nigericin. Graph symbols show average area under the curve (AUC) values relative to DMSO vehicle control for each cell type ± SEM from N = 2–4 independent experiments performed in duplicate.

BAL-0028 and BAL-0598 inhibit NLRP3-AID mutants. (A–F) IL-1β release assays from LPS and nigericin-stimulated PBMCs pre-treated with MCC950 (200, 1,000 nM) or BAL-0028 (200, 1,000 nM). Data from (A) healthy controls or patients with NLRP3-AID mutations (B) T348M, (C) A352V, (D and E) A439V, and (F) Y570C. Graph symbols show average IL-1β values ± SEM from N = 3 (A) or N = 1 (B–F) independent experiments performed in biological triplicate. (G) Comparison of BAL-0028 and MCC950 (40–1,000 nM) in a cell death assay in U937 cells expressing NLRP3 or NLRP3-AID mutants (D303H, A352V, L353P, K565E, E567G, K568N, G569R, and Y570C) stimulated with LPS and nigericin. Graph symbols show average area under the curve (AUC) values relative to DMSO vehicle control for each cell type ± SEM from N = 2–4 independent experiments performed in duplicate.

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