SRT-3025 is a potent and selective Sirt1 activator. It inhibits RANKL-induced osteoclast differentiation, fusion and resorptive capacity without affecting osteoclast survival. SRT-3025 inhibits RANKL-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs) by activating AMPK and deacetylating RelA/p65 lysine 310, critical for activation of the NF-κB signaling pathway.