JNKs (c-Jun N-terminal kinases) belong to mitogen-activated protein kinases' family and become activated by several growth factors, stress, radiation, and other extracellular signals. In turn, JNK activation results in phosphorylation of downstream molecules involved in many normal cellular processes[1]. JNK pathway regulates various physiological processes including inflammatory responses, cell differentiation, cell proliferation, cell death, cell survival and expression of proteins. Deregulation of JNK is linked with various diseases including neurodegenerative disease, autoimmune disease, diabetes, cancer, cardiac hypertrophy and asthma[2]. SU3327 is a potent, selective and substrate-competitive JNK inhibitor with an IC50 of 0.7 μM. SU3327 also inhibits protein-protein interactions between JNK and JNK Interacting Protein (JIP) with an IC50 of 239 nM. SU3327 shows less active against p38α and Akt kinase[3]. SU3327 is able to inhibit TNF-α stimulated phosphorylation of c-Jun in HeLa cells (EC50 = 6.23 μM). SU3327 (25 mg/kg; intraperitoneal injection; male BKS.Cg-+Leprdb/+Leprdb/OlaHsd db/db mice) treatment possesses the ability to restore insulin sensitivity in mice models of diabetes. SU3327 has favorable microsomal and plasma stability (T1/2 = 27 min)[4]. SU3327 (25 nM) pretreatment of human-derived cerebral microvascular endothelial cells (hCMEC/D3) effectively reduces LPS-induced polymorphonuclear leukocytes (PMN) rolling/adhesion to hCMEC/D3, prevents activation of AP-1, and significantly reduces expression of VCAM-1[5].
SU3327 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Actinobacillus pleuropneumoniae S6
2 μg/ml (MIC90)
24 hours
Evaluate the antibacterial activity of SU3327, showing significant antibacterial effects
Antibiotics (Basel). 2024 May 27;13(6):492
S. aureus ATCC 29213
8 µg/mL (MIC90)
24 hours
Evaluate the antibacterial activity of SU3327, showing significant antibacterial effects
Antibiotics (Basel). 2024 May 27;13(6):492
E. coli ATCC 25922
8 µg/mL (MIC90)
24 hours
Evaluate the antibacterial activity of SU3327, showing significant antibacterial effects
Antibiotics (Basel). 2024 May 27;13(6):492
H9c2 embryonic rat cardiomyocytes
10 µM
30 minutes
To evaluate the effects of SU3327 on cell viability, ROS levels, and mitochondrial membrane potential under H2O2-induced oxidative stress. Results showed that SU3327 increased cell death and ROS levels and decreased mitochondrial membrane potential.
SU3327 significantly downregulated serum ALT and AST levels at 16 h post CCl4 injection, and concurrently blocked the activation of cPLA2.
Sci Rep. 2020 Dec 17;10(1):22265
Male Sprague-Dawley rats
Isolated heart Langendorff perfusion model, 25 min global ischemia followed by 30 min reperfusion
Langendorff perfusion system
10 μM
Continuous perfusion for 25 min pre-ischemia and during 30 min reperfusion
To evaluate the effects of SU3327 on cardiac function and mitochondrial function. Results showed that SU3327 aggravated the recovery of heart function and reduced the mitochondrial respiratory control index.
PLoS One. 2014 Nov 25;9(11):e113526
Mice
Respiratory infection model
Oral
25.48, 12.74, 6.37 mg/kg b.w.
Single dose, lasting 48 hours
Evaluate the in vivo antibacterial activity of SU3327, showing effective treatment of respiratory infections
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