PROTACPI3K/110β degrader-2 is a selective PI3K/p110β PROTAC degrader. It effectively degrades the 110β protein and inhibits the expression of P-glycoprotein. Additionally, it increases reactive oxygen species (ROS) levels. PROTACPI3K/110β degrader-2 exerts antitumor effects by activating the endoplasmic reticulum stress (ERS) mediated mitochondrial apoptosis pathway and inhibiting the AKT/Bcl-2 signaling pathway. This compound is applicable in cancer research.

PROTAC PI3K/110β degrader-2 (Compound J-6) exhibits significant antitumor activity in A549 (IC50 = 58.2 μM), A549/DDP (IC50 = 39.23 μM), MCF-7 (IC50 = 53.99 μM), and MCF-7/ADM (IC50 = 38.73 μM) cell lines. This compound selectively degrades the 110β protein in MCF-7/ADM and A549/DDP cells in a time and concentration-dependent manner (0-50 μM, 0-48 hours). Furthermore, at concentrations of 0-25 μM for 24 hours, it markedly increases ROS levels, reduces mitochondrial membrane potential, and triggers ERS-mediated apoptosis in the same cell lines. Additionally, it inhibits Na+/K+-ATPase activity and decreases P-glycoprotein expression in MCF-7/ADM and A549/DDP cells.

Compound J-6, known as PROTAC PI3K/110β degrader-2, administered at a dosage of 50 mg/kg via intraperitoneal injection every other day for a total of 7 treatments, effectively inhibits tumor growth by degrading the 110β protein in female MCF-7/ADM tumor BALB/c mice.