PROTAC HER2 degrader-1

PROTAC HER2 degrader-1 (CH7C4) potently and selectively inhibits the activity of purified HER2 kinase with an IC₅₀ of 48.65 nM, while it exhibits much weaker inhibitory activity against EGFR kinase with an IC₅₀ of 4383 nM. It potently suppresses the proliferation of HER2-positive BT-474, SK-BR-3 and NCI-N87 cancer cells, with IC₅₀ values of 0.047 nM, 0.098 nM and 0.137 nM, respectively^[1].
PROTAC HER2 degrader-1 (0.078-10 μM; 72 h) does not inhibit the proliferation of EGFR-driven A431 cells^[1].
PROTAC HER2 degrader-1 (0.1-1000 nM; 1-24 h) efficiently induces concentration- and time-dependent HER2 degradation in BT-474 cells, with a DC₅₀ of 69 nM and a Dmax of 96%; it also induces such degradation in NCI-N87 cells, with a DC₅₀ of 55 nM and a Dmax of 94%^[1].
PROTAC HER2 degrader-1 (10-1000 nM; 0-24 h) potently and persistently inhibits the PI3K/AKT and RAS/RAF/ERK signaling pathways downstream of HER2 in BT-474 and NCI-N87 cells by inducing HER2 degradation^[1].
PROTAC HER2 degrader-1 (200 nM; 24 h) induces HER2 degradation in BT-474 cells via a ubiquitin-proteasome system-dependent mechanism. This process is blocked by UPS inhibitors, CRBN ligands and HER2 inhibitors, and is completely abolished by methylation of this agent^[1].