Shanghaitech University

Linyi Liu

Yan Li

Biao Jiang

Ning Sun

Jinju Chen

Ying Kong

Chaowei Ren

Xiaobao Yang

Xing Qiu

Qianqian Yin

Renhong Sun

Quanju Zhao

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor. 

Compounds targeting and degrading BCR-ABL protein and its antitumor application

Growing community of inventors

Shanghai, China

Linyi Liu