Design of KDM4 Inhibitors with Antiproliferative Effects in Cancer Models [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 636.99 Animal husbandry
• Thông tin xuất bản: Argonne, Ill. : Oak Ridge, Tenn. : Argonne National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2017
• Mô tả vật lý: Size: p. 869-874 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260419
• Chủ đề: 1. 60 applied life sciences; 2. Cancer; 3. Epigenetics; 4. Histone demethylase; 5. Jmjd2; 6. Kdm4; 7. Synthesis

Tóm tắt

Histone lysine demethylases (KDMs) play a vital role in the regulation of chromatin-related processes. In this paper, we describe our discovery of a series of potent KDM4 inhibitors that are both cell permeable and antiproliferative in cancer models. The modulation of histone H3K9me3 and H3K36me3 upon compound treatment was verified by homogeneous time-resolved fluorescence assay and by mass spectroscopy detection. Optimization of the series using structure-based drug design led to compound 6 (QC6352), a potent KDM4 family inhibitor that is efficacious in breast and colon cancer PDX models.