Title:
SELECTIVE HISTONE DEACETYLASE 8 DEGRADER, PREPARATION METHOD AND APPLICATION THEREOF IN ANTI-TUMOR ACTIVITY
Document Type and Number:
WIPO Patent Application WO/2023/151113
Kind Code:
A1
Abstract:
Disclosed are a selective histone deacetylase 8 (HDAC8) degrader, a preparation method and an application thereof in anti-tumor activity, relating to the technical field of drug design and synthesis. The selective HDAC8 degrader can significantly and selectively degrade HDAC8 in tumor cells in a concentration-dependent manner, without affecting other types of deacetylases, thereby prompting the value of the selective HDAC8 degrader in the preparation of drugs for preventing or treating diseases related to abnormal HDAC8 activity or expression, especially anti-tumor active drugs.
Inventors:
ZHU WEIGUO (CN)
HUANG JINBO (CN)
ZHANG JUN (CN)
XU WENCHAO (CN)
HUANG JINBO (CN)
ZHANG JUN (CN)
XU WENCHAO (CN)
Application Number:
PCT/CN2022/076987
Publication Date:
August 17, 2023
Filing Date:
February 21, 2022
Export Citation:
Assignee:
UNIV SHENZHEN (CN)
International Classes:
A61K31/4439; C07D401/14; A61P35/00
Domestic Patent References:
| WO2007109178A2 | 2007-09-27 |
Foreign References:
| US20200022966A1 | 2020-01-23 |
Other References:
YANG KA, WU HAO, ZHANG ZHONGRUI, LEISTEN ERIC D., NIE XUEQING, LIU BINKAI, WEN ZHI, ZHANG JING, CUNNINGHAM MICHAEL D., TANG WEIPIN: "Development of Selective Histone Deacetylase 6 (HDAC6) Degraders Recruiting Von Hippel–Lindau (VHL) E3 Ubiquitin Ligase", ACS MEDICINAL CHEMISTRY LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 11, no. 4, 9 April 2020 (2020-04-09), US , pages 575 - 581, XP055874848, ISSN: 1948-5875, DOI: 10.1021/acsmedchemlett.0c00046
WU HAO, YANG KA, ZHANG ZHONGRUI, LEISTEN ERIC D., LI ZIYUAN, XIE HAIBO, LIU JIN, SMITH KERRY A., NOVAKOVA ZORA, BARINKA CYRIL, TAN: "Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 62, no. 15, 8 August 2019 (2019-08-08), US , pages 7042 - 7057, XP055836747, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.9b00516
YANG KA, SONG YANLING, XIE HAIBO, WU HAO, WU YI-TING, LEISTEN ERIC D., TANG WEIPING: "Development of the first small molecule histone deacetylase 6 (HDAC6) degraders", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 28, no. 14, 1 August 2018 (2018-08-01), Amsterdam NL , pages 2493 - 2497, XP093084623, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2018.05.057
BALASUBRAMANIAN S; RAMOS J; LUO W; SIRISAWAD M; VERNER E; BUGGY J J: "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas", LEUKEMIA, NATURE PUBLISHING GROUP UK, LONDON, vol. 22, no. 5, 7 February 2008 (2008-02-07), London, pages 1026 - 1034, XP037785329, ISSN: 0887-6924, DOI: 10.1038/leu.2008.9
WU HAO, YANG KA, ZHANG ZHONGRUI, LEISTEN ERIC D., LI ZIYUAN, XIE HAIBO, LIU JIN, SMITH KERRY A., NOVAKOVA ZORA, BARINKA CYRIL, TAN: "Development of Multifunctional Histone Deacetylase 6 Degraders with Potent Antimyeloma Activity", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 62, no. 15, 8 August 2019 (2019-08-08), US , pages 7042 - 7057, XP055836747, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.9b00516
YANG KA, SONG YANLING, XIE HAIBO, WU HAO, WU YI-TING, LEISTEN ERIC D., TANG WEIPING: "Development of the first small molecule histone deacetylase 6 (HDAC6) degraders", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, ELSEVIER, AMSTERDAM NL, vol. 28, no. 14, 1 August 2018 (2018-08-01), Amsterdam NL , pages 2493 - 2497, XP093084623, ISSN: 0960-894X, DOI: 10.1016/j.bmcl.2018.05.057
BALASUBRAMANIAN S; RAMOS J; LUO W; SIRISAWAD M; VERNER E; BUGGY J J: "A novel histone deacetylase 8 (HDAC8)-specific inhibitor PCI-34051 induces apoptosis in T-cell lymphomas", LEUKEMIA, NATURE PUBLISHING GROUP UK, LONDON, vol. 22, no. 5, 7 February 2008 (2008-02-07), London, pages 1026 - 1034, XP037785329, ISSN: 0887-6924, DOI: 10.1038/leu.2008.9
Attorney, Agent or Firm:
SHENZHEN TALENT PATENT SERVICE (CN)
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