CEP 1347

Biological Activity

CEP 1347 is a potent inhibitor of mixed lineage kinases MLK3, MLK1 and MLK2 (IC₅₀ values in vitro are 23-39 nM, 38-61 nM and 51-82 nM, respectively), and blocks downstream c-jun N-terminal kinase (JNK) activation (IC₅₀ = 20 nM). CEP 1347 rescues motor neurons undergoing apoptosis (EC₅₀ = 20 nM), blocks Aβ-induced cortical neuron apoptosis (EC₅₀ ~51 nM) and, in an animal model of Huntington's disease, restores BDNF mRNA to wild type levels. CEP 1347 is also a MDM4 inhibitor. It displays inhibition of malignant meningioma cells growth in vitro, and shows anti-tumor activity in a mouse xenograft model of meningioma in vivo. CEP 1347 is orally bioavailable and brain penetrant.

Technical Data

The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.

Background References

1. Preservation of cholinergic activity and prevention of neuron death by CEP-1347/KT-7515 following excitotoxic injury of the nucleus basalis magnocellularis.
   Saporito et al.
   Neuroscience, 1998;86:461
2. Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway.
   Maroney et al.
   J.Neurosci., 1998;18:104
3. CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Abeta-induced cortical neuron apoptosis.
   Bozyczko-Coyne et al.
   J.Neurochem., 2001;77:849

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