AO-176 is a humanized anti-CD47 IgG2 monoclonal antibody. It induces tumor phagocytosis by blocking the interaction between CD47 and SIRPα. AO-176 preferentially binds to tumor cells over normal cells and directly kills tumor cells through a cell-autonomous mechanism, rather than via antibody-dependent cellular cytotoxicity (ADCC). In tumor xenograft models, AO-176 demonstrates dose-dependent antitumor activity. This compound is applicable in cancer research, such as studies involving lymphoma.

AO-176 exhibits different EC50 values against various cell lines: 130 ng/mL for OV90, 390 ng/mL for HCC827, 649 ng/mL for SNU-1, 250 ng/mL for OV10-315, 2700 ng/mL for MDA-MB-231, 390 ng/mL for Jurkat, and 1910 ng/mL for Raji. At a concentration of 10 μg/mL over 24 hours, AO-176 can induce cell death in Jurkat and OV90 cells. Its binding to red blood cells is negligible across a range of 0.017-1000 μg/mL and does not cause agglutination of washed human red blood cells. Additionally, it exhibits no cytotoxic effects on normal or activated T cells when used at 10-30 μg/mL for 24 hours. AO-176 directly inhibits the interaction between SIRPα and CD47 in Jurkat cells with an IC50 of 0.78 to 0.87 μg/mL after 90 minutes at concentrations of 0.001-100 μg/mL. Lastly, AO-176 facilitates the phagocytosis of Jurkat, Raji, OV90, Detroit 562, and FaDu cells in a concentration-dependent manner at 0.01-10 μg/mL over 2 hours.

AO-176, when administered intravenously at doses of 1-25 mg/kg once weekly for 4 weeks, significantly inhibits tumor growth in Raji lymphoma xenograft mouse models. Similarly, at doses of 10-25 mg/kg administered intraperitoneally once or five times per week for 5-6 weeks, AO-176 effectively suppresses tumor growth in MDA-MB-231, SNU-1, and OV90 xenograft tumors in mice. Furthermore, AO-176 demonstrates antitumor activity at 3-25 mg/kg in RPMI-8226 and NCI-H929 xenograft models.