Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Borrello, Maria Teresa¹  Schinor, Benjamin^2,3  Bartels, Katharina^2,3  Benelkebir, Hanae¹  Pereira, Sara¹  Al-Jamal, Wafa T.¹  Douglas, Leon⁴  Duriez, Patrick J.⁴  Packham, Graham⁴  Haufe, Guenter^2,3  Ganesan, A.¹ 

[1] Univ East Anglia, Sch Pharm, Norwich Res Pk, Norwich NR4 7TJ, Norfolk, England

[2] Univ Munster, Organ Chem Inst, Corrensstr 40, Munster, Germany

[3] Univ Munster, Cluster Excellence, Cells In Mot, Waldeyerstr 15, D-48149 Munster, Germany

[4] Univ Southampton, Canc Res UK Ctr, Univ Rd, Southampton SO17 1BJ, Hants, England

关键词: Organofluorine compounds;    Epigenetics;    FAD-dependent enzymes;    Lysine demethylase;    Mechanism based inhibitors;   

DOI  :  10.1016/j.bmcl.2017.03.081

来源: Elsevier

【 摘 要 】

We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p-substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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