PDF(Pubmed)
Abstract：
As the global population ages, the number of patients with osteoporosis is rapidly rising. The existing first-line clinical drugs are bone resorption inhibitors that have difficulty restoring the bone mass of elderly patients to the safe range. The range and period of use of existing peptides and monoclonal antibodies are limited, and small-molecule bone formation-promoting drugs are urgently required. We established an I-9 synthesis route with high yield, simple operation, and low cost that was suitable for future large-scale production. I-9 administration promoted bone formation and increased bone mass in mice with low bone mass in an aged C57 mouse model. Our findings revealed a hitherto undescribed pathway involving the BMP2-ERK-ATF4 axis that promotes osteoblast differentiation; I-9 has favorable biosafety in mice. This study systematically investigated the efficacy, safety, and mechanism of I-9 for treating osteoporosis and positions this drug for preclinical research in the future. Thus, this study has promoted the development of small-molecule bone-promoting drugs.
摘要：
随着全球人口老龄化,骨质疏松症患者的数量正在迅速增加。现有的一线临床药物均为骨吸收抑制剂，难以将老年患者的骨量恢复到安全范围。现有肽和单克隆抗体的使用范围和期限有限,迫切需要小分子骨形成促进药物。我们建立了高产率的I-9合成路线，操作简单,成本低，适合未来大规模生产。I-9给药在老年C57小鼠模型中促进骨形成和骨质量增加。我们的发现揭示了迄今为止尚未描述的涉及促进成骨细胞分化的BMP2-ERK-ATF4轴的途径；I-9在小鼠中具有良好的生物安全性。本研究系统地调查了疗效，安全,和I-9治疗骨质疏松症的机制，并将该药物用于未来的临床前研究。因此，这项研究促进了小分子促骨药物的发展。
