2. Academic Validation
  3. Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy

Discovery of Potential Neuroprotective Agents against Paclitaxel-Induced Peripheral Neuropathy

  • J Med Chem. 2022 Mar 24;65(6):4767-4782. doi: 10.1021/acs.jmedchem.1c01912.
Yi-Fan Chen 1 2,  Chien-Huang Wu 3,  Li-Hsien Chen 1,  Hao-Wei Lee 3,  Jinq-Chyi Lee 3,  Teng-Kuang Yeh 3,  Jang-Yang Chang 3,  Ming-Chen Chou 3,  Hui-Ling Wu 3,  Yen-Po Lai 3,  Jen-Shin Song 3,  Kai-Chia Yeh 3,  Chiung-Tong Chen 3,  Chia-Jui Lee 3,  Kak-Shan Shia 3,  Meng-Ru Shen 1 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan, R. O. C.
  • 2 Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan, R. O. C.
  • 3 Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli County 35053, Taiwan, R. O. C.
  • 4 Department of Obstetrics & Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City 70101, Taiwan, R. O. C.
PMID: 35234475 DOI: 10.1021/acs.jmedchem.1c01912
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.

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