紫杉醇（PTX）引起的化疗性周围神经病变（CIPN）是一种常见的副作用，影响30%至50%的患者。生存率的增加以及对患者生活质量的关注，推动了寻找预防PTX引起的神经病变的新工具。本研究介绍了神经核受体活化剂4-[(Z)-(2,4-二氧代-1,3-噻唑烷-5-基)甲基]-N-苯基苯磺酰胺（TZD-A1）作为PPARγ部分激动剂，其毒性学特点，以及其对PTX引起的CIPN在小鼠体内的影响。通过体外和体内生物分析评估了TZD-A1与PPARγ的相互作用。毒性学和药动学特性则借助体外、体内和体外实验进行评估。研究了TZD-A1对PTX注射小鼠的CIPN的影响。同时还评估了轴突和脊节神经节损伤、线粒体复合物活性、细胞因子水平、BDNF、Nrf2和PPARγ。通过对接分析预测TZD-A1与PPARγ的相互作用与部分激动剂兼容，体外实验报告验证了这一数据。通过体外、体内和体外实验，证实TZD-A1具有口服生物利用度和安全性。同时接受TZD-A1全身或口服治疗的PTX注射小鼠表现出机械和热敏感性的降低。TZD-A1的作用机制似乎是通过增加Nrf2和PPARγ水平以及BDNF基因上调来抑制神经炎症和线粒体损伤。部分活化PPARγ的TZD-A1能够引起神经保护作用并减轻PTX所引起的过敏反应。结合其良好的安全性和生物利用度，TZD-A1是防治癌症患者CIPN的一种有前景的药物候选物。本文受版权保护。保留所有权利。

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of paclitaxel (PTX), affecting 30 to 50% of patients. The increase in survival rate and the concern with patients' quality of life have encouraged the search for new tools to prevent PTX-induced neuropathy. This study presents the glitazone 4-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-N-phenylbenzene-sulfonamide (TZD-A1) as PPARγ partial-agonist, its toxicological profile, and effect on PTX-induced CIPN in mice.The interaction of TZD-A1 with PPARγ was tested using in silico docking analysis and in vitro reporter gene assay. The pharmacokinetics and toxicity were evaluated using in silico, in vitro and in vivo analysis. The effects of TZD-A1 on CIPN were investigated in PTX-injected mice. Axonal and DRG damage, mitochondrial complex activity, and cytokine levels, BDNF, Nrf2 and PPARγ were also evaluated.Docking analysis predicted TZD-A1 interaction with PPARγ compatible for partial agonists, data corroborated by the in vitro reporter gene assay. TZD-A1 presented oral bioavailability and safety profile evidenced by in silico, in vitro and in vivo experiments. PTX-injected mice, concomitantly treated with TZD-A1 by systemic or oral route, presented reduction of mechanical and thermal hypersensitivity. The mechanisms involved in TZD-A1 effect seem to be the inhibition of neuroinflammation and mitochondrial damage by increasing Nrf2 and PPARγ levels together with BDNF upregulation.TZD-A1, partially activating PPARγ, caused neuroprotection and reduced the hypersensitivity induced by PTX. Allied to its safety profile and good bioavailability, TZD-A1 is a promising drug candidate to prevent and treat CIPN in cancer patients.This article is protected by copyright. All rights reserved.