Title:
METHOD FOR DUAL-TARGET CONSTRUCTION OF PROTAC, AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2020/119192
Kind Code:
A1
Abstract:
A method for the dual-target construction of PROTAC and a specific construction method and use of dual-target PROTAC constructed using the method. The concept of dual-target design of PROTAC is proposed for the first time. That is, specific E3 is selected, and when PROTAC degrades target protein I, the degradation of an E3 natural substrate protein is impeded due to the contention of the PROTAC for the E3, i.e., the increase of target protein II. By using the method, the present invention constructs, for the first time, dual-target PROTAC that can not only target to the ubiquitination and degradation of Smad3 but also improve the HIF-α protein level. Theoretically, the dual-target PROTAC has a multi-path anti-fibrosis function and a renal protection function for treating renal anemia.
Inventors:
WANG XIN (CN)
ZHAO CHAO (CN)
YANG JIAYI (CN)
FAN JINJIN (CN)
FENG SHAOZHEN (CN)
LUO NING (CN)
ZHAO CHAO (CN)
YANG JIAYI (CN)
FAN JINJIN (CN)
FENG SHAOZHEN (CN)
LUO NING (CN)
Application Number:
PCT/CN2019/104264
Publication Date:
June 18, 2020
Filing Date:
September 04, 2019
Export Citation:
Assignee:
1ST AFFILIATED HOSPITAL SUN YAT SEN UNIV (CN)
International Classes:
C07K7/06; A61K38/05; C07K5/062; A61P7/06; A61P13/12
Domestic Patent References:
| WO2018204422A1 | 2018-11-08 |
Foreign References:
| CN109762045A | 2019-05-17 | |||
| CN105085620A | 2015-11-25 | |||
| CN105085620A | 2015-11-25 |
Other References:
WANG, XIN ET AL.: "New Strategy for Renal Fibrosis: Targeting Smad3 Proteins for Ubiquitination and Degradation", BIOCHEMICAL PHARMACOLOGY, vol. 116, 26 July 2016 (2016-07-26), XP029696561
GALDEANO, C. ET AL.: "Structure-Guided Design and Optimization of Small Molecules Targeting the Protein−Protein Interaction between the von Hippel−Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor(HIF) Alpha Subunit with in Vitro Nanomolar Affinities.", J. MED. CHEM., vol. 57, no. 20, 23 October 2014 (2014-10-23), pages 8657 - 8663, XP055235955
GALDEANO, C. ET AL.: "Structure-Guided Design and Optimization of Small Molecules Targeting the Protein−Protein Interaction between the von Hippel−Lindau (VHL) E3 Ubiquitin Ligase and the Hypoxia Inducible Factor(HIF) Alpha Subunit with in Vitro Nanomolar Affinities.", J. MED. CHEM., vol. 57, no. 20, 23 October 2014 (2014-10-23), pages 8657 - 8663, XP055235955
Attorney, Agent or Firm:
SCIHEAD IP LAW FIRM (CN)
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