2016年
Targeting Cancer with PCPA-Drug Conjugates: LSD1 Inhibition-Triggered Release of 4-Hydroxytamoxifen
Angewandte Chemie - International Edition
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- 巻
- 55
- 号
- 52
- 開始ページ
- 16115
- 終了ページ
- 16118
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/anie.201608711
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Targeting cancer with small molecule prodrugs should help overcome problems associated with conventional cancer-targeting methods. Herein, we focused on lysine-specific demethylase 1 (LSD1) to trigger the controlled release of anticancer drugs in cancer cells, where LSD1 is highly expressed. Conjugates of the LSD1 inhibitor trans-2-phenylcyclopropylamine (PCPA) were used as novel prodrugs to selectively release anticancer drugs by LSD1 inhibition. As PCPA-drug conjugate (PDC) prototypes, we designed PCPA-tamoxifen conjugates 1 a and 1 b, which released 4-hydroxytamoxifen in the presence of LSD1 in vitro. Furthermore, 1 a and 1 b inhibited the growth of breast cancer cells by the simultaneous inhibition of LSD1 and the estrogen receptor without exhibiting cytotoxicity toward normal cells. These results demonstrate that PDCs provide a useful prodrug method that may facilitate the selective release of drugs in cancer cells.
- リンク情報
- ID情報
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- DOI : 10.1002/anie.201608711
- ISSN : 1433-7851
- eISSN : 1521-3773
- PubMed ID : 27882656
- SCOPUS ID : 85006817474