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AMG161 is a fully human IgG1 monoclonal antibody developed by Amgen that targets receptor activator of nuclear factor kappa-B ligand (RANKL). Originally generated by immunizing XenoMouse models with human RANKL, AMG161 was designed to inhibit RANKL-RANK signaling. However, due to concerns that the IgG1 isotype could induce complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC) against RANKL-producing cells (such as osteoblasts, stromal cells, and T cells), Amgen converted the antibody to a non-cytotoxic IgG2 isotype, which became AMG 162 (denosumab). While AMG161 was not pursued for clinical development, it remains widely used in preclinical research as a tool to study RANKL-RANK signaling inhibition, particularly in humanized RANKL knock-in mouse models.
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