PROTACc-Met degrader-6 is a potent and orally active c-Met PROTAC degrader. It effectively promotes the degradation of c-Met protein, with DC50 values of 0.52 nM in EBC-1 cells and 0.45 nM in Hs746T cells. This compound almost completely abolishes the migration and invasion capabilities of tumor cells, significantly induces apoptosis (apoptosis), and arrests the cell cycle at the G0/G1 phase. PROTACc-Met degrader-6 is useful for studying various cancers, including non-small cell lung cancer and gastric cancer.

PROTAC c-Met degrader-6 (Compound G4) exhibits antiproliferative efficacy, showing IC50 values of 3.55, 3.01, and 7.48 nM in EBC-1, Hs746T, and MHCC97H cells, respectively. At concentrations of 1-10 nM over 48 hours, it significantly degrades c-Met via the ubiquitin-proteasome pathway in EBC-1 and Hs746T cells. Additionally, within the range of 5-10 nM for 24-48 hours, it powerfully induces apoptosis, causes G1 phase cell cycle arrest, and inhibits cell migration and invasion. At 100-1000 nM over 48 hours to 3 days, it shows excellent antiproliferative activity against EBC-1 and Hs746T cells carrying c-MetD1228N and c-MetY1230H mutations. Furthermore, PROTAC c-Met degrader-6 demonstrates good metabolic stability in human liver microsomes and mouse liver microsomes.

PROTAC c-Met degrader-6 (Compound G4) administered orally at a dosage of 5-10 mg/kg once daily for 18 days significantly inhibits tumor growth in the EBC-1 xenograft mouse model.