Uses
JNK Inhibitor V is an anti-inflammatory JNK inhibitor with neuroprotective properties. JNK Inhibitor V and Clofibrate (C586910) synergistically inhibit proliferation, induce apoptosis and differentiation via differential modulation of gene expression profile in human colon cancer cells.
Definition
ChEBI: 2-(1,3-benzothiazol-2-yl)-2-[2-[2-(3-pyridinyl)ethylamino]-4-pyrimidinyl]acetonitrile is a member of benzothiazoles.
Biological Activity
recent evidence suggests activation of the c-jun nh2-terminal protein kinase (jnk) signal transduction pathway may play a role in ischemia-induced cell death. therefore, preventing the activation of jnk, or c-jun phosphorylation could be neuroprotective. as601245 is a c-jun nh2-terminal protein kinase inhibitor.
in vitro
as601245 demonstrated a nonspecific inhibition of the three jnk human isoforms. as601245 inhibits isolated hjnk3 in an atpcompetitive manner. selectivity of as601245 was tested against a large panel of kinases. it exhibited 10- to 20-fold selectivity over c-src, cdk2, and c-raf and more than 50- to 100-fold selectivity over a range of tyr- and ser/thr-protein kinases [1].
in vivo
as601245 administered i.p. provided significant protection against the delayed loss of hippocampal ca1 neurons in a gerbil model of transient global ischemia. this effect is mediated by jnk inhibition and thus by c-jun expression and phosphorylation. a significant neuroprotective effect of as601245 administered either by i.p. injection or as i.v. bolus followed by an i.v. infusion was also observed in rats after focal cerebral ischemia [1].
IC 50
150, 220, and 70 nm for hjnk1, hjnk2, and hjnk3, respectively
References
[1] carboni s, hiver a, szyndralewiez c, gaillard p, gotteland jp, vitte pa. as601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-jun nh2-terminal protein kinase inhibitor with neuroprotective properties. j pharmacol exp ther. 2004 jul;310(1):25-32. epub 2004 feb 26.
