Enzymatic C42 Diversification of Rapamycin Identifies a Potent Butyryl-Modified Anticancer Derivative
A highly regioselective, one-step lipase-catalyzed method enabled the diversification of rapamycin at its C42 position, producing 10 derivatives (4 novel). Biological screening identified derivative <b>9</b> as a potent lead compound with superior antiproliferative activity (IC<sub>50</sub> = 6.5 μM in ACHN cells), outperforming both rapamycin and temsirolimus. This work offers a practical enzymatic route for rapamycin remodeling and highlights a promising mTOR-targeted anticancer candidate.
Authors
- Haiyan Pan (ORCID: https://orcid.org/0000-0002-5464-1642)
- Aiai Sun
- Gong-Li Tang
- Hengyu Li
- Yining Liu
- Jinyue Pu
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Zunyi Medical University (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Institute of Organic Chemistry (CN)
- ZheJiang Institute For Food and Drug Control (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-02-24
- DOI
- https://doi.org/10.1021/acs.orglett.6c00072
- Primary Topic
- PI3K/AKT/mTOR signaling in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00