izTRAIL is a newly available, highly active recombinant form of soluble human TRAIL. Due to a trimerizing N-terminal isoleucine zipper (iz) motif the intrinsic trimerization of TRAIL, required for apoptosis-inducing activity of TRAIL, is enhanced when compared to non-tagged soluble human TRAIL (shTRAIL). Therefore, izTRAIL is a potent inducer of apoptosis in many human cancer cells, but not normal human hepatocytes. In addition, the half-life of izTRAIL is about eight-fold higher than the half-life of shTRAIL. These properties render izTRAIL highly suitable for both, in vitro and in vivo use, particularly for studies in which investigators plan to transfer their in vitro results into an in vivo system with human cancer cells in xenotransplant settings examining susceptibility to TRAIL-induced apoptosis.
Biological Activity:Induces apoptosis in vitro in different human cancer cell lines with an EC50 of 5-200ng/ml, depending on the individual cell line used. Recombinant izTRAIL does not kill 4-day cultures of primary human hepatocytes (PHH) at concentrations of at least up to 1ug/ml (Ganten 2006). Good bioavailability in vivo, shows no toxic effects in mice at doses of at least up to 500ug per day (Wissink 2006).
Sequence:The extracellular domain of human TRAIL (aa95-281) is fused at the N-terminus to an isoleucine zipper motif.
Molecular Weight:~82kD as stable trimers (determined by size exclusion chromatography) ~28kD as monomer (determined by SDS-PAGE)
Specificity:Binds to human TRAIL receptors 1-4 (TRAIL-R1 to TRAIL-R4); izTRAIL does not interact with the apoptosis-inducing mouse TRAIL receptor (TRAIL-R).
Storage and Stability:Lyophilized and reconstituted products may be stored at -20°C. Stable for 6 months after receipt at -20°C. Reconstitute with sterile ddH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
