Fig. 2: Identification of F10 as a cardiac-specific allosteric myosin inhibitor.

a Single dose acto-myosin S1 ATPase activity screen of the 84 top ranking compounds from AI-based virtual screen. Hit thresholds are shown as red dashed lines. Means ± s.e.m. for n = 4 independent repeats, except for compounds #46 and #49 with n = 3 independent repeats. b Dose-response analysis for hit compound F10 on acto-myosin S1 ATPase activity. Means ± s.e.m., n = 6 independent repeats. c Chemical structure and physico-chemical properties of F10 (MW – molecular weight; log PO/W – partition coefficient octanol/water; LE – ligand efficiency). d F-Actin concentration-dependent bovine cardiac myosin S1 ATPase activity in the absence (black, vehicle control) and in the presence of 100 μmol/L F10 (red). Means ± s.e.m., n = 3 independent repeats for control and n = 9 independent repeats in the presence of F10. e ATPase activity of myofibrils isolated from cardiac, and fast and slow skeletal muscle in the absence (black) and in the presence of 20 μmol L-1 F10. Means ± s.e.m. for n = 20-23 experiments from n = 3 independent myofibril preparations. Statistical significance between control and drug treatment group was assessed with a two-tailed, unpaired student’s t-test for parametric data or Mann-Whitney test for non-parametric data sets. Source data are provided as a Source Data file.