PROTAC3

PROTAC3 (also known as Halo-PROTAC3) is a research-grade proteolysis-targeting chimera (PROTAC) designed to induce the degradation of proteins fused to a HaloTag. It is a heterobifunctional small molecule comprising a chloroalkane ligand, which binds covalently to the HaloTag, and a ligand for the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, joined by a chemical linker. By recruiting the VHL E3 ligase into close proximity with the HaloTag-fusion protein, PROTAC3 facilitates the polyubiquitination of the target protein, leading to its subsequent degradation by the 26S proteasome. This tool allows for the rapid, reversible, and dose-dependent depletion of specific proteins in living cells. In the context of hematologic research, PROTAC3 has been employed to study the role of the RNA helicase DDX41 in acute myeloid leukemia (AML) by degrading DDX41-HaloTag fusion proteins, thereby demonstrating that DDX41 loss leads to defects in granulocyte maturation and RNA splicing.

Other names

HaloTag-targeting PROTAC 3