PROTACHER2 degrader-1 is a highly selective HER2 PROTAC degrader with a DC50 of 69 nM and a Dmax of 96%. It effectively inhibits HER2-positive cell proliferation and tumor growth by inducing sustained HER2 degradation and strongly inhibiting downstream pathways (AKT and ERK). Additionally, PROTACHER2 degrader-1 can induce apoptosis in BT-474 cells and is useful for researching HER2-positive cancers.

HER2:69 nM (DC50)

PROTAC HER2 degrader-1 (Compound CH7C4) effectively degrades HER2 in BT-474 cells over a 24-hour period at concentrations between 0.1 to 3 μM, and demonstrates superiority over EGFR degradation in A431 cells. At concentrations up to 10 μM over 72 hours, it exhibits no inhibitory effect on the proliferation of A431 cells. The compound inhibits proliferation in HER2-driven breast cancer cell lines BT-474 and SK-BR-3, as well as in the gastric cancer cell line NCI-N87, with IC50 values of 0.047 nM, 0.098 nM, and 0.137 nM, respectively. In BT-474 cells, PROTAC HER2 degrader-1 (0-100 nM) induces apoptosis and inhibits the G1 phase of the cell cycle. It also induces HER2 degradation in a concentration-dependent manner in BT-474 (DC50 = 69 nM, Dmax = 96%) and NCI-N87 cells (DC50 = 55 nM, Dmax = 94%). Furthermore, at 200 nM over a 0-24 hour duration, the compound facilitates HER2 degradation in BT-474 and NCI-N87 cells, while inhibiting AKT and ERK phosphorylation. Finally, at 200 nM over 24 hours, it promotes ubiquitin-mediated HER2 degradation in BT-474 cells via the ubiquitin proteasome system (UPS).

PROTAC HER2 degrader-1 (Compound CH7C4) administered intravenously at doses of 5 mg/kg and 10 mg/kg once daily for 21 days effectively inhibits tumor growth in BALB/c nude mice bearing BT-474 xenograft tumors.