Enzymatic C42 Diversification of Rapamycin Identifies a Potent Butyryl-Modified Anticancer Derivative

Organic Letters 2026

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Authors: Yining Liu, Hengyu Li, Jinyue Pu, Aiai Sun, Hai‐Xue Pan, Gong‐Li Tang
DOI: 10.1021/acs.orglett.6c00072
Cited by: 0
References: 26

Abstract

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 9 as a potent lead compound with superior antiproliferative activity (IC 50 = 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.

Fields of Study & Subjects

Enzyme Catalysis and Immobilization PI3K/AKT/mTOR signaling in cancer Asymmetric Synthesis and Catalysis

Publication details

Journal / source
Organic Letters
Volume
28
Issue
9
Pages
2902–2905
Publication date
24 February 2026
Language
EN