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izTRAIL is a recombinant fusion protein designed to enhance the therapeutic potential of soluble human TRAIL (TNF-related apoptosis-inducing ligand). It incorporates an N-terminal isoleucine zipper (iz) motif that facilitates the stable trimerization of the TRAIL protein, a structural requirement for its biological activity. By mimicking the natural membrane-bound form of TRAIL, izTRAIL effectively binds and clusters death receptors DR4 (TRAIL-R1) and DR5 (TRAIL-R2) on the surface of cancer cells, thereby activating the extrinsic apoptotic pathway. Produced recombinantly in *E. coli*, izTRAIL has demonstrated potent in vitro activity against various malignancies, including colorectal cancer, fibrosarcoma, and head and neck squamous cell carcinoma. Despite its high activity in laboratory settings, its efficacy as a monotherapy in vivo is often limited by resistance mechanisms, leading to research into combination therapies with agents like sorafenib or dinaciclib to sensitize tumor cells to TRAIL-induced apoptosis.
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