Fig. 4: PROTAC 6 induces potent degradation of RIPK2 in human PBMCs and inhibits cytokine release in human disease tissue.
From: Extended pharmacodynamic responses observed upon PROTAC-mediated degradation of RIPK2
We tested the effect of PROTAC 6 on (a) RIPK2 levels at 6 and 24 h and (b) cytokine release following 3h pre-incubation and 3h L18-MDP stimulation in human PBMCs. Comparison of the effect of PROTAC 6 and negative control PROTAC 7 after 6h on (c) RIPK2 and (d) L18-MDP stimulated TNFα release in human PBMCs. Data are shown as mean ± s.e.m. (n = 6 except RIPK2 levels at 6h, n = 5). Spontaneous cytokine production from (e) CD and (f) UC disease patient intestinal biopsies (n = 5–19 per group) upon vehicle (DMSO) treatment (Ctrl) or treated with 1 µM prednisolone (P) or with increasing concentrations (0.05–50 nM) of PROTAC 6.
