AbMole丨SP600125：JNK抑制剂在细胞分化及动物模型中的应用

SP600125（JNK Inhibitor II，AbMole，M2076）是一种广泛应用于基础研究中的c-Jun N末端激酶（JNK）的特异性抑制剂，通过抑制JNK的磷酸化活性，调控下游如c-Jun、ATF-2等转录因子的活化，从而影响细胞凋亡、周期、分化及炎症反应等多种生物学过程。

在细胞实验中，SP600125（CAS No.：129-56-6）的使用浓度范围较广。例如，在人神经母细胞瘤SH-SY5Y细胞中，30 μM 的SP600125可显著抑制JNK磷酸化并保护细胞免受异氟烷诱导的损伤[1]；在MG-63和Saos-2骨肉瘤细胞中，5 μM的SP600125被用于细胞癌变机制研究[2]；SP600125（NSC75890）在大鼠心肌细胞H9c2中，以剂量依赖方式抑制高尿酸（HUA）诱导的脂肪积累及脂ogenic基因表达[3]；SP600125在MC3T3-E1成骨前体细胞中，可逆转镉诱导的Runx2下调并提升细胞存活率[4]；10 μM SP600125在人胶质母细胞瘤细胞（GBMCs）中，处理24小时后显著抑制增殖并上调HIF-1α与BMP4表达[5]；SP600125在MH7A类风湿关节炎滑膜成纤维细胞中，还能有效抑制MMP-3表达，提示JNK/MMP通路可能是关节炎研究的新靶点[6]；SP600125（1PMV）在肺上皮细胞中，能阻断AREG 诱导的c-Jun磷酸化及上皮-间质转化（EMT）过程[7]；在HPDLSCs（牙周膜干细胞）中，SP600125可逆转Wnt5a 对成骨分化的抑制作用[8]；SP600125在BMSCs（骨髓间充质干细胞）中，减轻TNF-α 诱导的p53、caspase-9/-3上调，改善细胞迁移能力[9]。

SP600125（JNK Inhibitor II）在动物实验中，常通过腹腔注射（i.p.）给药，少部分为脑室注射（i.c.v.）给药，剂量多为10–50 mg/kg。例如，在RAG-2−/−小鼠A673肉瘤模型中，50 mg/kg剂量显著抑制肿瘤生长并降低VEGF表达与微血管密度（MVD），同时提高凋亡指数[10]；在大鼠局灶性脑缺血再灌注（MCAO）模型中，i.c.v.给予SP600125可减轻脑梗死体积并改善行为异常[11]；SP600125在心肌缺血再灌注损伤大鼠模型中，与Ulinastatin（乌司他丁）联用可降低p-JNK表达并减少心肌细胞凋亡[12]。

综合来看，SP600125（AbMole，M2076）作为JNK通路的关键工具化合物，在多种细胞系（包括SH-SY5Y、U2OS、PC12等）及小鼠、大鼠等动物模型中，为解析JNK信号在细胞命运决定、应激响应及组织稳态维持中的作用提供了重要实验工具。

范例详解

Mol Med. 2025 May 15;31(1):190.

科研人员在上述文章中使用了AbMole的SP600125（M2076）。实验人员探究了脂质运载蛋白-2（LCN2）介导铁死亡机制在光诱导光感受器退化中的作用，结果显示：光暴露显著诱导LCN2在光感受器细胞和视网膜中的表达，LCN2通过增加细胞内Fe²⁺水平和激活JNK通路，抑制SLC7A11-GSH-GPX4轴，从而诱导铁死亡。SP600125是一种选择性JNK抑制剂，通过阻断JNK通路激活，证实了上述发现。

图 1. LCN2 regulated ferroptosis in 661 W photoreceptor cells by modulating the JNK pathway[13].

参考文献及鸣谢

[1] Yang, Z.; Lv, J.; Lu, X.; et al. Emulsified isoflurane induces release of cytochrome C in human neuroblastoma SHSY-5Y cells via JNK (c-Jun N-terminal kinases) signaling pathway. Neurotoxicology and teratology 2018, 65, 19-25.

[2] Wang, L.; Wang, J.; Chu, X.; et al. Cholesterol and steroid synthesis pathways may be involved in the inhibition of osteosarcoma cell viability by calcium-sensing receptor antagonism. PeerJ 2026, 14, e20546.

[3] Xie, D.; Zhao, H.; Lu, J.; et al. High uric acid induces liver fat accumulation via ROS/JNK/AP-1 signaling. American journal of physiology. Endocrinology and metabolism 2021, 320 (6), E1032-e1043.

[4] Ou, L.; Wang, H.; Wu, Z.; et al. Effects of cadmium on osteoblast cell line: Exportin 1 accumulation, p-JNK activation, DNA damage and cell apoptosis. Ecotoxicology and environmental safety 2021, 208, 111668.

[5] Kose, C.; Uslu, S.; Calik-Kocaturk, D.; et al. JNK Inhibition Modulates the Cytoskeleton, Hypoxia, and Neurogenesis on the Protein Level in Glioblastoma Cells and Astrocytes: An Immunofluorescence Study. Turkish neurosurgery 2023, 33 (6), 982-989.

[6] Kanai, T.; Kondo, N.; Okada, M.; et al. The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3. Journal of orthopaedic surgery and research 2020, 15 (1), 87.

[7] Cheng, W. H.; Kao, S. Y.; Chen, C. L.; et al. Amphiregulin induces CCN2 and fibronectin expression by TGF-β through EGFR-dependent pathway in lung epithelial cells. Respiratory research 2022, 23 (1), 381.

[8] Hasegawa, D.; Wada, N.; Yoshida, S.; et al. Wnt5a suppresses osteoblastic differentiation of human periodontal ligament stem cell-like cells via Ror2/JNK signaling. Journal of cellular physiology 2018, 233 (2), 1752-1762.

[9] Wei, B.; Bai, X.; Chen, K.; et al. SP600125 enhances the anti-apoptotic capacity and migration of bone marrow mesenchymal stem cells treated with tumor necrosis factor-alpha. Biochemical and biophysical research communications 2016, 475 (4), 301-307.

[10] Huang, Y. C.; Pan, W.; Li, H.; et al. c-Jun NH2-terminal kinase suppression significantly inhibits the growth of transplanted breast tumors in mice. The Journal of international medical research 2020, 48 (6), 300060520929858.

[11] Yamazaki, Y.; Arita, K.; Harada, S.; et al. Activation of c-Jun N-terminal kinase and p38 after cerebral ischemia upregulates cerebral sodium-glucose transporter type 1. Journal of pharmacological sciences 2018, 138 (4), 240-246.

[12] Yang, Z. H.; Lu, Y. J.; Gu, K. P.; et al. Effect of ulinastatin on myocardial ischemia-reperfusion injury through JNK and P38 MAPK signaling pathways. European review for medical and pharmacological sciences 2019, 23 (19), 8658-8664.

[13] Tang, W.; Zhai, R.; Ma, J.; et al. Lipocalin-2-mediated ferroptosis as a target for protection against light-induced photoreceptor degeneration. Molecular medicine (Cambridge, Mass.) 2025, 31 (1), 190.