ARGX-111 is a defucosylated anti-MET antibody that inhibits both HGF-dependent and HGF-independent signaling and reduces MET expression on tumor cell surfaces. It suppresses tumor metastasis by enhancing antibody-dependent cellular cytotoxicity (ADCC) to deplete MET-expressing circulating tumor cells. In metastatic breast cancer orthotopic mouse models, ARGX-111 has been shown to deplete circulating tumor cells and inhibit bone and lung metastases. This compound is suitable for research in cancers such as breast cancer.

ARGX-111 exhibits an EC50 range from 0.1 nmol/L to 0.7 nmol/L when binding with natural MET and competes with HGF with an IC50 of 1.3 nmol/L and IMAX of 95%. It inhibits HGF-induced MET autophosphorylation in A549 cells (IC50 = 5.3 nmol/L, IMAX = 74%) and in MKN-45 cells (IC50 = 0.2 nmol/L, IMAX = 63%), as well as in EBC-1 cells (IC50 = 12.7 nmol/L, IMAX = 69%). ARGX-111 neutralizes HGF’s pro-migratory effect, suppressing 78% of HGF-dependent colony formation in A549 cells. It also inhibits HGF-induced branching tubulogenesis in SV40 T antigen-transformed LOC human renal epithelial cell spheres at concentrations of 1-10 nM/L. Additionally, ARGX-111 promotes rapid reduction of MET expression in MKN-45, EBC-1, and MDA-MB 231 cells within 0.1-100 hours. Over a period of 24-48 hours, it does not promote MET receptor shedding but decreases total MET in MKN-45 cells. ARGX-111 induces dose-dependent cell lysis in MKN-45, NCI-H441, and A549 cells across 0-1000 nM/L. It also induces antibody-dependent cellular phagocytosis (ADCP) in MKN-45 and 786-O cells and facilitates dose-dependent antibody-dependent cellular cytotoxicity (ADCC) in ALDH-1 sorted MDA-MB-231, CRCM168, CRCM174, and CRCM389 cells from concentrations ranging from 0-667 nM/L.