PROTACHIF-1αdegrader-2 is a highly efficient and selective PROTAC degrader targeting HIF-1α. It facilitates the degradation of HIF-1α via the ubiquitin-proteasome pathway by promoting the formation of the HIF-1α/VHL ternary complex. This compound inhibits the proliferation, migration, and colony formation of HeLa cells while inducing apoptosis (apoptosis). Additionally, PROTACHIF-1αdegrader-2 reduces the expression of p-MEK and p-AKT in the MAPK and PI3K/AKT pathways. It is useful for cervical cancer research.

HIF1α:22.4 μM (DC50)

PROTAC HIF-1α degrader-2 (Compound Z12) exhibits significant antiproliferative activity against HeLa cells with an IC50 of 10.10 μM. In a dose-dependent manner, it degrades HIF-1α protein in HeLa cells (0-80 μM, 24 hours) with a DC50 of 22.40 μM, exhibiting a "hook effect" at concentrations over 40 μM. At 20 μM, it degrades HIF-1α in a time-dependent fashion, achieving a degradation rate of 59.7% after 36 hours of incubation, maintaining the effect for 24 hours post-removal of the compound. Over a period of 48 hours, at concentrations ranging from 0 to 20 μM, the compound induces acute cytotoxicity in HeLa cells, reducing live cells (green fluorescence) and increasing dead cells (red fluorescence) in a dose-dependent manner. It also inhibits colony formation in HeLa cells over 15 days at concentrations between 0 and 10 μM in a dose-dependent manner. Additionally, PROTAC HIF-1α degrader-2 impedes the migratory ability of HeLa cells (0-20 μM, 0-24 hours)and induces apoptosis in HeLa cells, causing morphological changes and increasing apoptotic rates at 0-20 μM over 24-48 hours. Furthermore, it reduces protein levels of p-MEK (44.6%-89.1%) and p-AKT (39.0%-63.0%) dose-dependently in HeLa cells within 24 hours.