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.