Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD). (15th June 2022)

• Record Type: Journal Article
• Authors: Lu, Jianyu; Chan, Chi-chung; Sun, Deheng; Hu, Guoping; He, Huijun; Li, Jian; Dong, Jiaqiang; Liu, Kai; Shen, Liang; Hu, Lihong; Gu, Qingyang; Chen, Shuhui; Wang, Tielin; Gong, Ting; Tang, Wei; Li, Xiaoting; Zhu, Xiaotong; Zeng, Xu; Zhu, Yingjie; Xia, Yuanfeng; Huang, Yuanyuan; Zhu, Yusong; Liu, Zhenteng; Ding, Charles Z.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 66(2022)
• Publication Date: 2022-06-15
• Subjects: Estrogen receptor -- SERD -- Indole; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2022.128734
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: We previously described the discovery of a novel indole series compounds as oral SERD for ER positive breast cancer treatment. Further SAR exploration focusing on substitutions on indole moiety of compound 12 led to the discovery of a clinical candidate LX-039. We report herein its profound anti-tumor activity, desirable ER antagonistic characteristics combined with favorable pharmacokinetic and preliminary safety properties. LX-039 is currently in clinical trial (NCT04097756).