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].
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