Title:
TARGETED PROTEIN DEGRADATION-BASED C-MET DEGRADING AGENT, AND PREPARATION METHOD THEREFOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2022/082876
Kind Code:
A1
Abstract:
A c-Met degrading agent based on a targeted protein degradation PROTAC strategy and a preparation method therefor, and the use of such c-Met degrading agents in the treatment of non-small cell lung cancer, gastric cancer and other cancers. The degrading agent has significant effects on degrading c-Met and inhibiting cell proliferation, has a potential to be used as an anti-tumor drug to treat tumors, and exhibits significant activity of inhibiting proliferation in a EBC-1 drug-resistant cell line constructed by means of lentivirus transfection, and same is obviously better than a small molecule inhibitor LXM-262, and significantly improves the cell selectivity, indicating that the compound has a significant advantage in overcoming an acquired drug resistance of c-Met in a tumor. In particular, compound S27 only shows better activity on c-Met-dependent EBC-1 lung cancer cells, indicating that compound S27 has better cell selectivity, while the original small molecule inhibitor is multi-targeted and the compound also has an inhibitory effect on c-Met-independent cell lines.
Inventors:
LONG YAQIU (CN)
WANG XU (CN)
FENG SHUN (CN)
WANG XU (CN)
FENG SHUN (CN)
Application Number:
PCT/CN2020/126904
Publication Date:
April 28, 2022
Filing Date:
November 06, 2020
Export Citation:
Assignee:
UNIV SOOCHOW (CN)
International Classes:
C07D471/04; A61K31/454; A61K31/4545; A61K38/05; A61K38/06; A61K38/07; A61K45/06; A61P35/00; A61P35/02; C07D401/04; C07D401/12; C07K5/062; C07K5/097; C07K5/103
Domestic Patent References:
| WO2018226542A1 | 2018-12-13 | |||
| WO2016184434A1 | 2016-11-24 |
Foreign References:
| CN108366992A | 2018-08-03 | |||
| CN111285849A | 2020-06-16 | |||
| CN110769822A | 2020-02-07 |
Other References:
GUO ZIYU, ET AL: "Recent Advance of Small Molecular VEGFR-2 Inhibitors for Cancer Treatment", CHINESE JOURNAL OF BIOCHEMICAL PHARMACEUTICS, QUANGUO SHENGHUA ZHIYAO QINGBAO ZHONGXINZHAN, NANJING, CN, vol. 35, no. 6, 31 December 2015 (2015-12-31), CN , pages 176 - 180, XP055924566, ISSN: 1005-1678
Attorney, Agent or Firm:
CENTRAL SOUTH WELL INTELLECTUAL PROPERTY OFFICE (CN)
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