Cascade class I new drug CS0159 was approved for clinical research

Recently, Cascade Pharmaceuticals, Inc announced that the clinical trial application of the new FXR agonist CS0159 for the indications of primary sclerosing cholangitis (PSC) jointly developed by the company's founder Eric Xu team of Shanghai Institute of pharmac。

CS0159 is a new powerful non steroidal farnesol X receptor (FXR) small molecule agonist based on crystal structure aided design. Based on the deep understanding of the structure and mechanism of the interaction between FXR target and drugs, the research team designed and synthesized a series of lead compounds, and systematically evaluated the drug efficacy, toxicology and pharmacokinetics of the compounds in vivo and in vitro, and finally obtained the new drug candidate compound CS0159. The innovation of the project is to make full use of protein structure aided design, find the action sites that can enhance drug activity and reduce drug side effects, and apply them to the molecular design of new drugs.

       Crystal structure of FXR - cs0159 complex

Systematic preclinical studies have shown that, CS0159 has the characteristics of strong FXR agonistic activity and liver targeted distribution. It can significantly improve the pathological condition of 3,5-diethyloxycarbonyl-1,4-dihydrotrimethylpyridine (DDC) - induced PSC model in mice. It has the characteristics of low effective dose, significant efficacy and good tolerance. Its clinical trial is approved, which is expected to provide safe and effective potential treatment options for PSC patients.