2. Academic Validation
  3. Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile

Identification of N-(((1S,3R,5S)-adamantan-1-yl)methyl)-3-((4-chlorophenyl)sulfonyl)benzenesulfonamide as novel Nav1.8 inhibitor with analgesic profile

  • Bioorg Med Chem Lett. 2024 Jun 27:110:129862. doi: 10.1016/j.bmcl.2024.129862.
Chi Song 1,  Jie Qiu 1,  Menglan Luo 1,  Yihang Fu 1,  Shilong Hu 1,  Wencheng Liu 1,  Di Zhang 1,  Meiyuan Chen 1,  Zhihua Cao 1,  Xi Yang 2,  Bowen Ke 3
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China.
  • 2 Department of Anesthesiology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
  • 3 Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041 Sichuan, China. Electronic address: bowenke@scu.edu.cn.
PMID: 38944398 DOI: 10.1016/j.bmcl.2024.129862
Abstract

Chronic pain is a common and challenging clinical problem that significantly impacts patients' quality of life. The Sodium Channel Nav1.8 plays a crucial role in the occurrence and development of chronic pain, making it one of the key targets for treating chronic pain. In this article, we combined virtual screening with cell membrane chromatography techniques to establish a novel method for rapid high-throughput screening of selective Nav1.8 inhibitors. Using this approach, we identified a small molecule compound 6, which not only demonstrated high affinity and inhibitory activity against Nav1.8 but also exhibited significant inhibitory effects on CFA-induced chronic inflammatory pain. Compared to the positive drug VX-150, compound 6 showed a more prolonged analgesic effect, making it a promising candidate as a Nav1.8 inhibitor with potential clinical applications. This discovery provides a new therapeutic option for the treatment of chronic pain.

Keywords

Chronic pain; Inflammatory pain; Nav1.8; Virtual screening.

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