DT2216

DT2216 is a small molecule proteolysis-targeting chimera (PROTAC) that selectively degrades the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL). It consists of a Bcl-XL ligand linked to a Von Hippel-Lindau (VHL) E3 ligase ligand. Upon administration, it binds to Bcl-XL in tumor cells and regulatory T-cells within the tumor microenvironment, recruiting VHL E3 ligase to tag Bcl-XL for ubiquitination and subsequent proteasomal degradation. This process inhibits the anti-apoptotic function of Bcl-XL, restores apoptosis in cancer cells dependent on this protein for survival, and reduces immunosuppressive regulatory T-cells. Unlike other Bcl-XL inhibitors, DT2216 spares platelets due to low VHL expression in these cells. The drug is being developed primarily for hematologic malignancies such as T-cell lymphoma and has received orphan drug designation from the FDA[1][4][7][8].

Other names

Bcl-XL proteolysis targeting chimera DT2216