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Updated: May 24, 2026

Development and Application of Rapamycin-regulated Tyrosine Phosphatases
Published on: September 6, 2024
Tyrosyl-DNA phosphodiesterase 1 inhibitor from an anamorphic fungus
Motoki Takagi1, Jun-ya Ueda, Ji-Hwan Hwang
1Biomedicinal Information Research Center (BIRC), Japan Biological Informatics Consortium (JBIC), 2-4-7 Aomi, Tokyo 135-0064, Japan. motoki-takagi@aist.go.jp
Abstract:
Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is an enzyme that catalyzes hydrolysis of 3'-phosphotyrosyl bonds and is involved in repair of irreversible topoisomerase I (Top1)-DNA covalent complexes. Tdp1 inhibitors are regarded as potential cancer therapeutics in combination with Top1 inhibitors, which are currently used to treat human cancers. While screening for Tdp1 inhibitors, we discovered a novel compound, JBIR-21 (1), from the culture of an anamorphic fungus, RF-13305. The structure of 1 was established by extensive NMR and MS analyses. Compound 1 showed inhibitory activity against Tdp1 (IC(50) value, 18 μM) and cytotoxic activity against cancer cell lines (IC(50) values, 3.5-13 μM). Compound 1 also exhibited antitumor activity in a mouse xenograft model without adverse effects.
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