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Papers of the Week

Papers: 13 Jan 2024 - 19 Jan 2024

2024 Jan 18

J Med Chem


Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality.


Chen Y, Sun J, Tong H, Wang J, Cao R, Xu H, Chen L, Morisseau C, Zhang M, Shi Y, Han C, Zhuang J, Jing Y, Liu Z, Hammock BD, Chen G


Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound . exhibits selective inhibition of HDAC6 over class I HDACs in cells. shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than . improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.