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R1FasL is a recombinant homotrimeric fusion protein designed to convert vascular endothelial growth factor (VEGF) from a pro-angiogenic tumor factor into a pro-apoptotic signal. The molecule is composed of the VEGF-binding domain of human VEGFR1 (Flt-1) fused to the trimerization and death receptor-binding domains of human Fas ligand (FasL). In the tumor microenvironment, overexpressed VEGF binds to the VEGFR1 domain of R1FasL, acting as a molecular bridge that crosslinks the fusion proteins into higher-order complexes. These clustered complexes then aggregate and activate Fas (CD95) death receptors on the surface of tumor or stromal cells, triggering the extrinsic apoptotic pathway. This "trap-and-kill" strategy aims to simultaneously neutralize the pro-angiogenic effects of VEGF and selectively induce cell death within the tumor microenvironment.
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