2. Academic Validation
  3. Synthesis and Biological Evaluation of β-Lactam Derivatives Targeting Speckle-Type POZ Protein (SPOP)

Synthesis and Biological Evaluation of β-Lactam Derivatives Targeting Speckle-Type POZ Protein (SPOP)

  • ACS Med Chem Lett. 2024 Jan 25;15(2):270-279. doi: 10.1021/acsmedchemlett.3c00515.
Chenmao Zhou 1,  Xinyue Hao 1,  Zhengyang Chen 2 3,  Runze Zhang 2 3,  Qian Zhou 1 2,  Zisheng Fan 4 2,  Mingyue Zheng 2 3 1,  Hui Hou 2 3,  Sulin Zhang 2 3,  Hao Guo 5
Affiliations

Affiliations

  • 1 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Drug Discovery and Design Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.
  • 5 Birdo (Shanghai) Pharmatech Co., Ltd, Shanghai 201318, China.
PMID: 38352842 DOI: 10.1021/acsmedchemlett.3c00515
Abstract

Speckle-type POZ protein (SPOP) acts as a cullin3-RING ubiquitin ligase adaptor, which facilitates the recognition and ubiquitination of substrate proteins. Previous research suggests that targeting SPOP holds promise in the treatment of clear cell renal cell carcinoma (ccRCC). On the basis of the reported SPOP inhibitor 230D7, a series of β-lactam derivatives were synthesized in this study. The biological activity assessment of these compounds revealed E1 as the most potent inhibitor, which can disrupt the SPOP-substrate interactions in vitro and suppress the colony formation of ccRCC cells. Taken together, this study provided compound E1 as a potent inhibitor against ccRCC and offered insight into the development of the β-lactam SPOP inhibitor.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-161251
    SPOP Inhibitor