Dong Lu, Jianwei Chen, Li Qin, Imani Bijou, Ping Yi, Feng Li, Xianzhou Song, Kevin R MacKenzie, Xin Yu, Bin Yang, Sandipan Roy Chowdhury, James D Korp, Bert W O'Malley, David M Lonard, Jin Wang
Steroid receptor coactivator 3 (SRC-3) is a critical mediator of many intracellular signaling pathways that are crucial for cancer proliferation and metastasis. In this study, we performed structure-activity relationship exploration and drug-like optimization of the hit compound SI-2 , guided by in vitro / in vivo metabolism studies and cytotoxicity assays. Our efforts led to the discovery of two lead compounds, SI-10 and SI-12 . Both compounds exhibit potent cytotoxicity against a panel of human cancer cell lines and demonstrate acceptable pharmacokinetic properties...
March 29, 2024: Journal of Medicinal Chemistry