PI3K Degrader

PROTAC PI3K/110β degrader-1 is a VHL-recruiting PROTAC degrader targeting PI3K/110β, with DC₅₀ values of 0.416 μM (MCF-7) and 19.66 μM (A549), respectively. PROTAC PI3K/110β degrader-1 recruits VHL to induce proteasomal degradation of PI3K/110β. It activates endoplasmic reticulum stress (ERS)-mediated mitochondrial apoptosis via the PERK/ATF4/CHOP unfolded protein response (UPR) pathway, downregulates p-AKT and Bcl-2, upregulates Bax, cleaved-caspase-9 and cleaved-caspase-3, inhibits the expression and activity of P-gp, and exerts synergistic anti-tumor effects with Doxorubicin (Adriamycin, ADM) (HY-15142A) and Cisplatin (DDP) (HY-17394). PROTAC PI3K/110β degrader-1 can be used in research related to multidrug-resistant cancers.

PROTAC PI3K/110β degrader-2 is a VHL-recruiting PI3K/110β PROTAC degrader, with DC₅₀ values of 1.258 μM and 2.185 μM in MCF-7/ADM and A549/DDP cells, respectively. PROTAC PI3K/110β degrader-2 induces proteasomal degradation of PI3K/110β, inhibits phosphorylation of AKT and expression of Bcl-2, while suppressing the activity and expression of P-gp. It also induces endoplasmic reticulum stress and mitochondrial apoptosis via the PERK/CHOP pathway. PROTAC PI3K/110β degrader-2 exerts anti-tumor activity against multidrug-resistant cancer cells both in vitro and in vivo, and produces a synergistic effect when combined with Doxorubicin (HY-15142A) or Cisplatin (HY-17394), making it applicable for the research of multidrug-resistant cancers.