2. Academic Validation
  3. Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents

Discovery of Selenium-Containing STING Agonists as Orally Available Antitumor Agents

  • J Med Chem. 2022 Sep 7. doi: 10.1021/acs.jmedchem.2c00634.
Xi Feng 1,  Lixia Pan 2,  Zhiyu Qian 1,  Dongyu Liu 1,  Xin Guan 2,  Li Feng,  Bin Song 1,  Xi Xu 1,  Ninghua Tan 1,  Yi Ma 1,  Zhiyu Li 1,  Zhe Wang 1,  Jinlei Bian 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of Medicinal Chemistry, Department of TCMs Pharmaceuticals, China Pharmaceutical University, Nanjing 211100, P. R. China.
  • 2 State Key Laboratory of Non-Food Biomass and Enzyme Technology, Guangxi Academy of Sciences, Nanning 530007, P. R. China.
PMID: 36069713 DOI: 10.1021/acs.jmedchem.2c00634
Abstract

Activation of the stimulator of interferon genes (STING) pathway to achieve antitumor response is an attractive approach for Cancer Immunotherapy. In this study, we report the identification of BSP16 (LF250) as a potent, orally available STING agonist. BSP16 strongly activates STING signaling in human and mouse cells and binds STING as a homodimer. A 2.4 Å cocrystal structure revealed that BSP16 could induce the "closed" conformation of STING. In vivo studies revealed that BSP16 is well tolerated, has an excellent pharmacokinetic profile as an oral drug, and induces tumor regression and durable antitumor immunity. The promising bioactivities of BSP16 make it valuable for further development as an antitumor agent.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-151264
    STING Agonist