Figure 1. In silico identifies GPVI antagonists.

Representative image capture of in silico docking into GPVI using Glide, with space filling model is shown in a, and H-bonding to relevant side chains is detailed in b. The 20 highest ranking compounds were screened for effects on Ca²⁺ release by the GPVI-specific agonist CRP-XL (10 µg/ml) (c and d, % refers to percent inhibition of Ca²⁺ release). Maximum Ca²⁺ release is shown in white, compounds that inhibited Ca²⁺ release by ∼50% or more are in grey, and the remainder in black. Commercially available compounds that inhibited CRP-XL-induced Ca²⁺ release >50% were further screened by light transmission aggregometry to identify compounds displaying dose-dependent inhibition (e-j). Examples are shown of weak antagonism (g and h) and false positives (i and j). Cinanserin (l) and losartan (k) were taken on for further study.