Impaired locomotion has been extensively studied worldwide because those afflicted with it have a potential risk of becoming bedridden. Physical exercise at times can be an effective remedy for frailty, but exercise therapy cannot be applied in all clinical cases. Medication is safer than exercise, but there are no drugs that reinforce both muscle and bone when administered alone. Multiple medications increase the risk of adverse events; thus, there is a need for individual drugs targeting both tissues. To this end, we established a novel sequential drug screening system and identified an aminoindazole derivative, locamidazole (LAMZ), which promotes both myogenesis and osteoblastogenesis while suppressing osteoclastogenesis. Administration of this drug enhanced locomotor function, with muscle and bone significantly strengthened. Mechanistically, LAMZ induced Mef2c and PGC-1α in a calcium signaling–dependent manner. As this signaling is activated upon physical exercise, LAMZ mimics physical exercise. Thus, LAMZ is a promising therapeutic drug for locomotor diseases, including sarcopenia and osteoporosis.

运动障碍已在世界范围内得到广泛研究，因为受此影响的人有卧床不起的潜在风险。体育锻炼有时可以是治疗虚弱的有效方法，但运动疗法并非适用于所有临床病例。药物治疗比运动更安全，但没有药物单独服用时可以同时增强肌肉和骨骼。多种药物会增加不良事件的风险；因此，需要针对两种组织的单独药物。为此，我们建立了一种新的序贯药物筛选系统，并鉴定了一种氨基吲唑衍生物洛咪唑（LAMZ），它在抑制破骨细胞生成的同时促进肌生成和成骨细胞生成。这种药物的施用增强了运动功能，肌肉和骨骼显着增强。机械地，LAMZ 以钙信号依赖的方式诱导 Mef2c 和 PGC-1α。由于这种信号在体育锻炼时被激活，LAMZ 模仿体育锻炼。因此，LAMZ 是一种很有前途的运动疾病治疗药物，包括肌肉减少症和骨质疏松症。