#Recombinant Human Insulin ; #10-365 ;
Biomed Pharmacother. 2024 Jun 20:177:116972.
Wenmin Chen 1, Yue Wu 2, Chuanyu Yang 3, Wenlong Ren 4, Lei Hou 5, Huichun Liang 3, Tingyue Wu 4, Yanjie Kong 6, Jiao Wu 7, Yu Rao 8, Ceshi Chen 9
Affiliations expand
- PMID: 38906024
- DOI: 10.1016/j.biopha.2024.116972
Free article
Abstract
Breast cancer is one of the most prevalent malignancies affecting women worldwide, underscoring the urgent need for more effective and specific treatments. Proteolysis-targeting chimeras (PROTACs) have emerged as a promising strategy to develop new lead compounds by selectively targeting oncoproteins for degradation. In this study, we designed, synthesized and evaluated a CRBN-based PROTAC, L055, which targets CDK9. Our findings demonstrate that L055 effectively inhibits the proliferation, induces cell cycle arrest, and decreases the survival of ERα-positive breast cancer cells in vitro. L055 specifically binds to CDK9, facilitating its degradation via the CRBN-dependent proteasomal pathway. Additionally, L055 suppressed the growth of organoids and tumors derived from T47D and MCF7 cells in nude mice. Thus, L055 represents a potential novel therapeutic agent for ERα-positive breast cancer and potentially other malignancies.