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A highly HDAC6-selective inhibitor acts as a fluorescent probe.
Ho, Yi-Hsun; Wang, Kuang-Jui; Hung, Pei-Yun; Cheng, Yi-Sheng; Liu, Jia-Rong; Fung, Sheang-Tze; Liang, Pi-Hui; Chern, Ji-Wang; Yu, Chao-Wu.
Afiliación
  • Ho YH; School of Pharmacy, College of Medicine, and Center for Innovative Therapeutics Discovery, National Taiwan University, Taipei 100, Taiwan. jwchern@ntu.edu.tw.
Org Biomol Chem ; 16(42): 7820-7832, 2018 10 31.
Article en En | MEDLINE | ID: mdl-30168823
HDAC6 receives great attention because of its therapeutic potential for the treatment of various diseases. Selective fluorescence imaging for HDAC6 is important for its pathological and biological studies. However, specific detection of HDAC6 by using a fluorescent small molecule probe remains a great challenge. Herein, a series of fluorescent HDAC6-selective inhibitors incorporating a naphthalimide skeleton were designed and synthesized. A structure-activity relationship study identified that compound JW-1 had the greatest inhibitory activity and superior specificity against HDAC6. JW-1 could substantially increase α-tubulin acetylation and was active against a panel of six cancer cell lines. Photophysical characterization and cellular imaging of MDA-MB-231 cells demonstrated that JW-1 is a highly fluorescent, cell penetrable, small-molecule inhibitor of HDAC6 that can be used for the detection of HDAC6 in complex cellular environments.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Histona Desacetilasas / Colorantes Fluorescentes / Histona Desacetilasa 6 Límite: Humans Idioma: En Revista: Org Biomol Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Histona Desacetilasas / Colorantes Fluorescentes / Histona Desacetilasa 6 Límite: Humans Idioma: En Revista: Org Biomol Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2018 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Reino Unido