Discovery of 1 H -Imidazo[4,5- b ]pyridine Derivatives as Potent and Selective BET Inhibitors for the Management of Neuropathic Pain.
Journal of medicinal chemistry(2023)
摘要
Neuropathic pain (NP) is an intolerable pain syndrome that arises from continuous inflammation and excitability after nerve injury. Only a few NP therapeutics are currently available, and all of them do not provide adequate pain relief. Herein, we report the discovery of a selective and potent inhibitor of the bromodomain and extra-terminal (BET) proteins for reducing neuroinflammation and excitability to treat NP. Starting with the screening hit from an in-house compound library, iterative optimization resulted in the potent BET inhibitor with a unique binding mode and a novel chemical structure. exhibits excellent BET selectivity and favorable drug-like properties. In mice with spared nerve injury, significantly alleviated mechanical hypersensitivity by inhibiting pro-inflammatory cytokine expression and reducing excitability. Collectively, these results implicate that is a promising agent for the treatment of NP.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要