DT388IL3[K116W]

DT388IL3[K116W] (also known as SL-501) is an experimental recombinant fusion toxin designed to target the interleukin-3 receptor (IL-3R), specifically the alpha subunit (CD123), which is highly expressed on acute myeloid leukemia (AML) cells and leukemic stem cells. The molecule is a second-generation version of tagraxofusp (SL-401), consisting of a truncated form of diphtheria toxin (DT388) fused to a human interleukin-3 (IL-3) variant. The DT388 component contains the catalytic and translocation domains but lacks the native cell-binding domain. The IL-3 moiety features a lysine-to-tryptophan substitution at position 116 (K116W), a modification engineered to significantly enhance binding affinity to the IL-3 receptor. Upon binding to CD123, the fusion protein is internalized via receptor-mediated endocytosis. The toxin's catalytic domain then escapes into the cytosol, where it inhibits protein synthesis by ADP-ribosylating eukaryotic translation elongation factor 2 (EEF2), ultimately leading to apoptosis of the leukemic cells.

Other names

High-affinity DT388IL3K116W variant of DT388IL3K-116W variant of DT388IL3K 116W variant of DT388IL3