HISTONE DEACETYLASE 6 INHIBITORS AND USE THEREOF

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

16/302,021

專利證號

US 11,427,544 B2

專利獲證名稱

HISTONE DEACETYLASE 6 INHIBITORS AND USE THEREOF

專利所屬機關 (申請機關)

臺北醫學大學

獲證日期

2022/08/30

技術說明

本發明係基於7-氮雜吲哚化合物可有效抑制HDAC6之發現。其對多種癌細胞(例如，口腔癌、非小細胞肺癌、前列腺癌、大腸直腸癌等)的抑制生長能力強也對HDAC的抑制能力強(IC50 = 0.1 μM)，其中，抑制HDAC6的選擇性高，為HDAC1之60倍、HDAC2之223倍。於動物試驗中，此化合物顯示對大腸直腸癌有明顯抑制生長之能力，比上市藥物SAHA強。 A series of indolylsulfonylcinnamic hydroxamates has been synthesized. (E)-3-(3-((1H- pyrrolo[2,3-b]pyridin-1-yl)sulfonyl)phenyl)-N-hydroxyacrylamide, which has a 7-azaindole core cap, was shown to have antiproliferative activity against KB, H460, PC3, HSC-3, HONE-1, A549, MCF-7, TSGH, MKN45, HT29, and HCT116 human cancer cell lines. Pharmacological studies indicated that it functions as a potent HDAC inhibitor with an IC50 value of 0.1 μM. It is highly selective for histone deacetylase 6 (HDAC6) and is 60-fold more active than against HDAC1 and 223-fold more active than against HDAC2. In in vivo efficacy evaluations in colorectal HCT116 xenografts, it suppresses tumor growth more effectively than SAHA and is therefore seen as a suitable candidate for further investigation.

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