Nstpbp5185, a novel benzimidazole derivative, suppresses PDGF signaling and reduces neointimal hyperplasia following vascular injury.

Restenosis remains a significant clinical challenge following percutaneous coronary interventions such as angioplasty and stenting. Despite advances in techniques and drug-eluting stents, neointimal hyperplasia and vessel re-narrowing still occur in many patients. Platelet-derived growth factor (PDGF) plays a crucial role in restenosis by promoting the migration and proliferation of vascular smooth muscle cells (VSMCs). We previously demonstrated that nstpbp5185, an orally bioavailable thromboxane A2 receptor (TP receptor) antagonist, exhibits anti-platelet, anti-thrombotic, and anti-atherosclerotic effects in murine models. In this study, we investigated whether nstpbp5185 could attenuate restenosis after vascular injury. In vitro, nstpbp5185 dose-dependently inhibited PDGF-stimulated VSMC migration and proliferation, reduced phosphorylation of PDGF receptor and downstream signaling molecules, and markedly suppressed PDGF-induced reactive oxygen species production. In vivo, nstpbp5185 significantly reduced neointimal formation and plasma levels of thromboxane B2 in a rat carotid artery balloon injury model. Furthermore, nstpbp5185 suppressed VSMC proliferation in response to U46619, a TP receptor agonist, and inhibited U46619-induced platelet aggregation in platelet-rich plasma from treated rats. These findings suggest that nstpbp5185 effectively reduces restenosis by inhibiting PDGF signaling and antagonizing the TXA2-mediated response, supporting its potential as a therapeutic candidate for preventing restenosis after coronary intervention.