Biological Activity
cep-1347, also called kt 7515, is an inhibitor of the c-jun n-terminal kinase (jnk) signaling pathway, with an ic50 value for jnk1 activation of 20 ± 2 nm in rat embryonic motoneurons [1].the jnk pathway, also known as the stress-activated protein kinase (sapk) pathway, is one of the signaling cascades that mediate the apoptotic death in response to a variety of stressful stimuli. jnk activation by phosphorylation is important for neuronal cell death after injury in vivo and after trophic factor withdrawal in vitro [2].cep-1347 induced neuronal survival. jnk1 activity in untreated cell cultures increased approximately fourfold within 24 hr after plating. as early as 15 min after the application of cep-1347 at 500 nm, the activity of jnk1 sharply decreased to ~50% of control levels. for the next 24 hr, the activity of jnk1 continued to decrease. cultures rich in motoneurons were grown in the presence of cep-1347 at increasing concentrations, and the ic50 for jnk1 activity at 22 hr was 21 ± 2 nm, whereas the ec50 for cell survival at 5 d was 20 ± 2 nm [1].cep-1347 can affect noise-induced hearing loss. data showed that hearing thresholds 2 d before noise exposure showed no significant difference between the noise-exposed control and treated group. hearing threshold shifts in all guinea pigs 2 d after the noise exposure. by day 6 after exposure, threshold shifts were significantly less in the cep-1347 group than in the noise-exposed control group. by 2 weeks after exposure, the difference between the two groups became more pronounced [2].
References
[1]. maroney ac, glicksman ma, basma an, et al. motoneuron apoptosis is blocked by cep-1347 (kt 7515), a novel inhibitor of the jnk signaling pathway[j]. the journal of neuroscience, 1998, 18(1): 104-111.
[2]. pirvola u, liang xq, virkkala j, et al. rescue of hearing, auditory hair cells, and neurons by cep-1347/kt7515, an inhibitor of c-jun n-terminal kinase activation[j]. the journal of neuroscience, 2000, 20(1): 43-50.
