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  • A recombinant fusion protein composed of the human C-propeptide of alpha1(I) collagen (Trimer-Tag) to the C-terminus of the mature human tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL; Apo2L), with potential pro-apoptotic and antineoplastic activities. The binding of TRAIL to the Trimer-Tag allows TRAIL to form a stable covalently-linked homotrimer. Upon administration of recombinant human TRAIL-trimer fusion protein SCB-313, this fusion protein targets, binds to and trimerizes the TRAIL-receptors, pro-apoptotic death receptors (DRs) TRAIL-R1 (death receptor 4; DR4) and TRAIL-R2 (death receptor 5; DR5), expressed on tumor cells, thereby activating caspases and inducing apoptosis in TRAIL-R1/R2-expressing tumor cells. TRAIL, a homotrimeric type II transmembrane protein and member of the TNF superfamily of cytokines, plays a key role in the induction of apoptosis through TRAIL-mediated death receptor pathways. The pro-apoptotic cell surface receptors TRAIL-R1 and -R2, members of the TNF receptor family, are overexpressed by a variety of cancer cell types; The induction of receptor trimerization is needed for the initiation of the apoptotic signaling pathway. The TRAIL-Trimer retains similar bioactivity and receptor binding kinetics as native TRAIL but has more favorable pharmacokinetics and antitumor activity than native TRAIL.
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