SP 600125

SP 600125 is an orally active, reversible, selective, ATP-competitive JNK inhibitor with IC₅₀ of 40, 40, and 90 nM for JNK1, JNK2, and JNK3, respectively. SP 600125 is commonly used in the research of ovarian cancer, tumors, Parkinson's disease (PD), breast cancer, and asthma^[1,2].

SP 600125 (10-20 μM; 24 h) reduces PMA-dependent MMP-9 secretion and inhibits c-Jun phosphorylation, and also inhibits PMA-stimulated MMP-9 promoter-driven luciferase reporter gene activity^[1].SP 600125 inhibits c-Jun phosphorylation with an IC₅₀ of 5-10 μM. SP 600125(5-10 μM,24h) also inhibits LPS-induced increase COX-2 protein levels and PGE2 production^[3].

SP 600125 (10/30/50 mg/kg/day; ip) inhibits MPTP-induced JNK activation and c-Jun phosphorylation in the substantia nigra obturata (SNc) and prevents the decrease in dopamine concentration in the striatum and alleviates behavioral impairment in MPTP-treated mice^[2]. SP 600125(30mg/kg/day) can significantly reduce the expression of inflammatory cells in the bronchi and lungs under OVA stimulation^[4].

References:
[1]. Shin M, Yan C, Boyd D. An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding and PMA-inducible 92-kDa type IV collagenase expression. Biochim Biophys Acta. 2002 May 8;1589(3):311-6.
[2]. Wang W, Shi L, Xie Y, Ma C, Li W, Su X, Huang S, Chen R, Zhu Z, Mao Z, Han Y, Li M. SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurosci Res. 2004 Feb;48(2):195-202.
[3]. Nieminen R, Lahti A, Jalonen U, Kankaanranta H, Moilanen E. JNK inhibitor SP600125 reduces COX-2 expression by attenuating mRNA in activated murine J774 macrophages. Int Immunopharmacol. 2006 Jun;6(6):987-96.
[4].Wu HM, Fang L, Shen QY, Liu RY. SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. Mol Immunol. 2015 Oct;67(2 Pt B):311-6.

SP 600125是一种具有口服活性的、可逆的、具有选择性的ATP竞争性JNK 抑制剂，对JNK1、JNK2和JNK3的IC₅₀分别为40、40和90nM。SP 600125常用于卵巢癌、肿瘤、帕金森病 (PD)、乳腺癌和哮喘的研究^[1,2]。

SP 600125 （10-20 μM；24 小时） 可降低 PMA 依赖的 MMP-9 分泌并抑制 c-Jun 磷酸化，还可抑制 PMA 刺激的 MMP-9 启动子驱动的荧光素酶报告基因活性^[1]。SP600125 抑制 c-Jun 磷酸化的 IC₅₀ 为 5-10 μM，SP600125（5-10 μM，24 小时）还可抑制 LPS 诱导的 COX-2 蛋白水平上升和 PGE2 产生^[3]。

SP 600125(10/30/50 mg/kg/day；ip)可抑制MPTP诱导的黑质闭孔(SNc)中JNK活化和c-Jun磷酸化，防止纹状体多巴胺浓度下降，减轻MPTP治疗小鼠的行为障碍^[2]。SP600125（30mg/kg/day）可显著减少OVA刺激下支气管和肺脏中炎症细胞的表达^[4]。