Hemorrhagic stroke occurs when a weakened vessel ruptures and bleeds into the surrounding brain, leading to high rates of deathand disability worldwide. A series of complex pathophysiological cascades contribute to the risk of hemorrhagic stroke, and notherapies have proven effective to prevent hemorrhagic stroke. Stabilization of vascular integrity has been considered as a potentialtherapeutic target for hemorrhagic stroke. ROCKs, which belong to the serine/threonine protein kinase family and participate in theorganization of actin cytoskeleton, have become attractive targets for the treatment of strokes. In this study,in vitroenzyme-basedassays revealed that a new compound (FPND) with a novel scaffold identified by docking-based virtual screening could inhibitROCK1 specifically at low micromolar concentration. Molecular modeling showed that FPND preferentially interacted with ROCK1,and the difference between the binding affinity of FPND toward ROCK1 and ROCK2 primarily resulted from non-polar contributions.Furthermore, FPND significantly prevented statin-induced cerebral hemorrhage in a zebrafish model. In addition,in vitrostudiesusing the xCELLigence RTCA system, immunofluorescence and western blotting revealed that FPND prevented statin-inducedcerebral hemorrhage by enhancing endothelial cell–cell junctions through inhibiting the ROCK-mediated VE-cadherin signalingpathway. As indicated by the extremely low toxicity of FPND against mice, it is safe and can potentially prevent vascular integrityloss-related diseases, such as hemorrhagic stroke.