Title:
APPLICATION OF LIGAND SMALL MOLECULE TARGETING PDCD4 IN PREPARATION OF ANTIDEPRESSANT DRUGS
Document Type and Number:
WIPO Patent Application WO/2022/246930
Kind Code:
A1
Abstract:
A compound, a pharmaceutical composition, and an application in preparation of anti-neurodegenerative disease drugs. Existing studies show that BDNF is an important therapeutic target for neurodegenerative diseases such as depression, and however, currently, there is a lack of effective drugs capable of acting directly on BDNF in the art. The inventor studied previous studies of the team, and finds that accumulation of PDCD4 can promote occurrence of depression by competitively binding to eIF4A to negatively regulate BDNF expression. On the basis of this mechanism, the inventor could conceive of screening PDCD4 ligand small molecules to promote BDNF expression, so as to realize the therapeutic effect. By means of screening, a compound AI-204 and a compound AG-690 can reverse the inhibition effect of PDCD4 overexpression and nerve cell mTORC1 inactivation on BDNF, up-regulate expression of BDNF in vitro, relieve chronic stress-induced depression-like behaviors, and are expected to be developed into therapeutic drugs for neurodegenerative diseases such as depression.
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Inventors:
ZHANG LINING (CN)
JIA YUFENG (CN)
LI YUAN (CN)
WANG QUN (CN)
LI YAN (CN)
ZHU FALIANG (CN)
GUO CHUN (CN)
JIA YUFENG (CN)
LI YUAN (CN)
WANG QUN (CN)
LI YAN (CN)
ZHU FALIANG (CN)
GUO CHUN (CN)
Application Number:
PCT/CN2021/100804
Publication Date:
December 01, 2022
Filing Date:
June 18, 2021
Export Citation:
Assignee:
UNIV SHANDONG (CN)
International Classes:
C07D487/04; A61P25/24; C07D213/87
Foreign References:
| CN110256574A | 2019-09-20 | |||
| CN107012203A | 2017-08-04 |
Other References:
WANG SHENGYUN, JUN-YING LIU, LV WANG, LI-WEI DUAN, QI-TONG CHEN, JIN-HAO ZHENG, ZHAO-FEN LIN, WEN-FANG LI : "Targeting programmed cell death 4 (PDCD4) with biogenic compounds in ARDS by Gaussian process‐based QSAR virtual screening", JOURNAL OF CHEMOMETRICS, vol. 30, no. 10, 14 September 2016 (2016-09-14), pages 621 - 627, XP093008792, DOI: 10.1002/cem.2827
LI, YUAN ET AL.: "Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression", MOLECULAR PSYCHIATRY, vol. 26, 16 March 2020 (2020-03-16), XP037563750, DOI: 10.1038/s41380-020-0692-x
JIA YUFENG, CHEN XIAOTONG, ZHANG LINING: "Role of PDCD4 in inflammation and tumors: a double-edged sword", SCIENCE CHINA: CHINESE BULLETIN OF LIFE SCIENCE = SCIENTIA SINICA VITAE, vol. 48, no. 11, 1 November 2018 (2018-11-01), pages 1217 - 1228, XP093008760, ISSN: 1674-7232, DOI: 10.1360/N052018-00164
JIANG YANFANG, YU XIN, LU LAIJIN, LIU ZHIGANG, YANG TENG, GONG XU, NING YUBO: "Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation", NEUROPSYCHIATRIC DISEASE AND TREATMENT, 29 March 2016 (2016-03-29), pages 685, XP093008789, DOI: 10.2147/NDT.S98387
GONG, HAOLING ET AL.: "High-throughput screening against-6.1 million structurally diverse, lead-like compounds to discover novel ROCK inhibitors for cerebral injury recovery", MOLECULAR DIVERSITY, vol. 20, 23 December 2015 (2015-12-23), XP035923930, DOI: 10.1007/s11030-015-9650-y
LI, YUAN ET AL.: "Programmed cell death 4 as an endogenous suppressor of BDNF translation is involved in stress-induced depression", MOLECULAR PSYCHIATRY, vol. 26, 16 March 2020 (2020-03-16), XP037563750, DOI: 10.1038/s41380-020-0692-x
JIA YUFENG, CHEN XIAOTONG, ZHANG LINING: "Role of PDCD4 in inflammation and tumors: a double-edged sword", SCIENCE CHINA: CHINESE BULLETIN OF LIFE SCIENCE = SCIENTIA SINICA VITAE, vol. 48, no. 11, 1 November 2018 (2018-11-01), pages 1217 - 1228, XP093008760, ISSN: 1674-7232, DOI: 10.1360/N052018-00164
JIANG YANFANG, YU XIN, LU LAIJIN, LIU ZHIGANG, YANG TENG, GONG XU, NING YUBO: "Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation", NEUROPSYCHIATRIC DISEASE AND TREATMENT, 29 March 2016 (2016-03-29), pages 685, XP093008789, DOI: 10.2147/NDT.S98387
GONG, HAOLING ET AL.: "High-throughput screening against-6.1 million structurally diverse, lead-like compounds to discover novel ROCK inhibitors for cerebral injury recovery", MOLECULAR DIVERSITY, vol. 20, 23 December 2015 (2015-12-23), XP035923930, DOI: 10.1007/s11030-015-9650-y
Attorney, Agent or Firm:
JINAN SHENGDA INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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