Advanced PROTAC and Quantitative Proteomics Strategy Reveals Bax Inhibitor-1 as a Critical Target of Icaritin in Burkitt Lymphoma.

ABSTRACT: Understanding the molecular targets of natural products is crucial for elucidating their mechanisms of action, mitigating toxicity, and uncovering potential therapeutic pathways. Icaritin (ICT), a bioactive flavonoid, demonstrates significant anti-tumor activity but lacks defined molecular targets. This study employs an advanced strategy integrating proteolysis targeting chimera (PROTAC) technology with quantitative proteomics to identify ICT's key targets. A library of 22 ICT-based PROTAC derivatives were synthesized, among which LJ-41 exhibited a superior IC50 of 5.52 μM against Burkitt lymphoma (CA-46) cells. Then, differential proteomic analysis identified Bax inhibitor-1 (BI-1) as a potential target. Target validation techniques, including cellular thermal shift assay (CETSA),

SUBMITTER: Zhang P 

PROVIDER: S-EPMC11641208 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature