Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangdong Provincial Second Hospital of Traditional Chinese Medicine (Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine), Guangzhou 510095, China.
Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
J Med Chem. 2024 Sep 12;67(17):15311-15327. doi: 10.1021/acs.jmedchem.4c00909. Epub 2024 Aug 21.
Developing a dual-efficiency agent with antiresorptive and anabolic applications is a promising strategy for treating osteoporosis. This study reports the discovery of dual antiosteoporosis agents a chemotype-assembly approach. Chemotype analysis identified 12 antiresorptive and 12 anabolic chemotypes and 7 dual-function chemotype-assembly rules. Based on these assembly rules, a dual-functional compound was discovered. exhibits osteoclastogenesis inhibition with an IC value of 10.28 μM and osteoblast differentiation stimulation at 10 μM. derivatives were designed and synthesized based on the activity relationship of the chemotypes. This yielded a more active compound, , with an osteoclastogenesis inhibition IC value of 0.40 μM and osteoblast differentiation stimulation at 1.0 μM; compound also suppressed bone loss . These results prove that can be a potential lead for antiosteoporosis drug development.
开发具有抗吸收和合成作用的双重功效剂是治疗骨质疏松症的一种有前途的策略。本研究报告了双重抗骨质疏松剂的发现——一种基于化学型组装的方法。化学型分析确定了 12 种抗吸收和 12 种合成化学型以及 7 种双功能化学型组装规则。基于这些组装规则，发现了一种双功能化合物 。 对破骨细胞生成的抑制作用，IC 值为 10.28 μM，对成骨细胞分化的刺激作用为 10 μM。根据化学型的活性关系设计并合成了 衍生物。这得到了一种更有效的化合物 ，对破骨细胞生成的抑制作用，IC 值为 0.40 μM，对成骨细胞分化的刺激作用为 1.0 μM；化合物 也抑制了骨丢失 。这些结果证明 可以成为抗骨质疏松药物开发的潜在先导化合物。
