Catalyst Awardee

Project Description

Study of the anti-osteoporosis effect and mechanism of IMB-E0924G as a dual regulator for bone resorption and formation

Yanni Xu, PhD | Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC); Shuyi Si, PhD
Competition Sponsor: Chinese Academy of Medical Sciences
Awardee Year: 2022

With the extending lifespan and accelerating population ageing, osteoporosis (OP) has become a major health problem affecting life quality and lifespan in elderly population. The side effects and limitations of existing osteoporosis drugs including antiresorptive agents and anabolic agents) affect its long-term application and compliance clinically. Efforts to develop small molecule drugs through inhibiting bone resorption and stimulating bone formation are critical to achieve normal bone turnover and bone dynamic balance and finally to improve the life quality of OP patients. Our research group have involved in the screening and discovery of novel anti-osteoporosis drugs. Previous studies have found compound E09241 can regulate OPG/RANKL and Wnt/β-Catenin signaling pathway. Additionally, E09241 has been found to inhibit bone resorption and promote bone formation, and has potent antiosteoporosis effect in ovariectomized (OVX) rats. IMB-E0924G is derivative of E09241 obtained through structural optimization, which are highly potential to develop as novel antiosteoporosis drug due to its optimal pharmacokinetic and low toxicity. In this study, we will use molecular biology technology for the research on mechanism of IMB-E0924G in up-regulating OPG expression. Alizarin red staining, RNAseq, and other assays will be used to investigate the activity of IMB-E0924G in promoting osteogenesis and inhibiting osteoclast differentiation in vitro. Moreover, in vivo study will be conducted with OVX rats in order to study the antiosteoporosis effect. Furthermore, preclinical studies including pharmacokinetics, synthetic technology, and dosage form selection, will be conducted. The implementation of this project will finally obtain an anti-osteoporosis drug candidate with independent intellectual property right.


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