Design and structurally analysis of sFLT01-based novel tri-specific molecule with antiangiogenic activity.

Age-related macular degeneration (AMD) refers to the progressive degeneration of the macula that commonly occurs in people over 60 years of age. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF-A) plays a pivotal role in formation of choroidal neovascularization. Anti-VEGF agents represent the current standard of care for neovascular age-related macular degeneration (nAMD). There are however still a proportion of patients who do not respond to conventional therapy. One possible explanation for the high rate of non-responders is that an anti-VEGF monotherapy only blocks one pathway of pathological angiogenesis and other angiogenic factors may be responsible for the disease progression.Methods: Therefore, the complimentary combinations of agents that inhibit alternative mechanisms of blood vessel formation may optimize inhibition of angiogenesis and improve clinical benefit for patients. sFLT01 is a dual targeting agent that neutralizes both VEGF and PlGF.Results: We designed a sFLT01-based novel tri-specific molecule that targets VEGF-A, PlGF and another angiogenic factor that is very important in the formation of new blood vessels. then we analyzed the secondary and tertiary structures of the tri-specific molecule.Conclusion: It is believed that targeting several angiogenic pathways by sFLT01-based novel tri-specific molecule has potential as a next-generation antiangiogenic therapeutic for age-related macular degeneration.