Class I new drug CS0159 was approved to enter clinical research

On October 20, 2021, the clinical trial application (IND) for primary sclerosing cholangitis (PSC) indication for the new class I drug CS0159 oral tablet was approved by the U.
S.
Food and Drug Administration (FDA)
.
CS0159 is a new type of powerful non-steroidal farnesoid X receptor (FXR) small molecule agonist based on crystal structure-assisted design.
It was independently developed by the Shanghai Institute of Medicine Xu Huaqiang's research group and Li Jia's research group.
Class I new drugs
.
CS0159 was transferred by Shanghai Institute of Medicine and Van Andel Institute in the form of exclusive license to Kaisikadi (Shanghai) Pharmaceutical Technology Co.
, Ltd.
for global R&D and promotion in 2020
.
The Xu Huaqiang team of the Shanghai Institute of Medicine has conducted in-depth research on the mechanism of nuclear hormone receptor drugs for more than 20 years; Li Jia’s team has long been committed to the research and development of innovative drugs for metabolic diseases, focusing on metabolic diseases such as diabetes and non-alcoholic steatohepatitis.
The disease has established a multi-target integration, multi-functional screening and multi-level efficacy evaluation system
.
Based on a deep understanding of the structure and mechanism of the interaction between the FXR target and the drug, the research team designed and synthesized a series of lead compounds, and evaluated the compound's efficacy, toxicology and pharmacokinetics in vivo and in vitro.
Obtained new drug candidate compound CS0159
.
The innovation of this project is to make full use of protein structure-assisted design, discover the sites of action that can enhance drug activity and reduce drug side effects, and apply them to the design of new drug molecules
.
FXR-CS0159 complex crystal structureSystematic preclinical studies have shown that CS0159 has potent FXR agonistic activity and the characteristics of liver targeting distribution, which can significantly improve the induction of 3,5-diethoxycarbonyl-1,4-dihydrocolumidine (DDC) The pathological condition of the mouse PSC model has the characteristics of low effective dose, significant drug effect and good tolerability.
The approval of its clinical trial is expected to provide safe and effective potential treatment options for PSC patients
.
The research and development of CS0159 has also been strongly supported by researcher Mei Xuefeng, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Researcher Chen Xiaoyan, Researcher Diao Xingxing, Researcher Gao Zhaobing, Research Center of Neuropsychiatric Diseases and other research groups
.
(Contribution department: Xu Huaqiang's research group, Li Jia's research group)