Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy.
Basic Information
ID: ALA5154771
Journal: J Med Chem
Title: Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy.
Authors: Chen YF, Wu CH, Chen LH, Lee HW, Lee JC, Yeh TK, Chang JY, Chou MC, Wu HL, Lai YP, Song JS, Yeh KC, Chen CT, Lee CJ, Shia KS, Shen MR.
Abstract: Chemotherapy-induced neurotoxicity is a common adverse effect of cancer treatment. No medication has been shown to be effective in the prevention or treatment of chemotherapy-induced neurotoxicity. Using minoxidil as an initial template for structural modifications in conjunction with an in vitro neurite outgrowth assay, an image-based high-content screening platform, and mouse behavior models, an effective neuroprotective agent CN016 was discovered. Our results showed that CN016 could inhibit paclitaxel-induced inflammatory responses and infiltration of immune cells into sensory neurons significantly. Thus, the suppression of proinflammatory factors elucidates, in part, the mechanism of action of CN016 on alleviating paclitaxel-induced peripheral neuropathy. Based on excellent efficacy in improving behavioral functions, high safety profiles (MTD > 500 mg/kg), and a large therapeutic window (MTD/MED > 50) in mice, CN016 might have great potential to become a peripherally neuroprotective agent to prevent neurotoxicity caused by chemotherapeutics as typified by paclitaxel.
CiteXplore: 35234475
DOI: 10.1021/acs.jmedchem.1c01912
Patent ID: ┄