AD4 is an artemisinin-derived proteolysis targeting chimera that selectively degrades PCLAF protein with subnanomolar potency in RS4;11 leukemia cells,AD4 leads to activation of the p21/Rb signaling axis, robust anti-tumor activity, and significantly prolonged survival in RS4;11 xenograft NOD/SCID mouse models, demonstrating both in vitro and in vivo therapeutic efficacy.

AD4 functions as a bifunctional PROTAC that recruits an E3 ubiquitin ligase to the PCLAF protein. Mechanistically, it utilizes an Artemisinin-based scaffold as a warhead to bind PCLAF, facilitating its proximity to the E3 ligase. This interaction leads to the polyubiquitination of PCLAF and its subsequent degradation via the proteasome pathway. In cellular assays, AD4 exhibits an IC50 of 0.6 nM against PCLAF. The depletion of PCLAF levels results in the disruption of DNA repair mechanisms and the suppression of tumor cell proliferation [1].

DMSO: 80 mg/mL (77.28 mM), Sonication is recommended.