CEP-1347  (Synonyms: KT7515)

CEP-1347 is an inhibitor of the JNK/SAPK pathway with neuroprotective effects. CEP-1347 blocks JNK1 activation induced by members of the mixed lineage kinase (MLK) family (MLK3, MLK2, MLK1, dual leucine zipper kinase, and leucine zipper kinase). As an inhibitor of MDM4, CEP-1347 can more effectively inhibit the growth of glioma cells expressing wild-type p53^{[1][2][3][4][5][6]}.

CEP-1347 (0-500 nM; 3 days) decreases the expression of MDM4 and activates the p53 pathway in malignant meningioma cells with wild-type p53^[4].
CEP-1347 (KT7515) promotes motor neuron survival by inhibiting JNK1 activity in rat embryonic motor neurons deficient in nutritional factors. The IC₅₀ values of CP-1347 for JNK1 activation and EC₅₀ values of motor neuron survival are both 20 nM^[5].
CEP-1347 (0.2-20 μM; 2 h) dose-dependently inhibits pancresin-induced JNK activation in isolated pancreatic acinus, and is almost completely effective at a concentration of 2 μM^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

CEP-1347 (0-60 mg/kg; Subcutaneous injection (s.c.)) in rats treated with Caerulein (HY-A0190) (10 μg/kg; Intravenous injection (i.v.)) can dose-dependent inhibit Caerulein Induced JNK activation and improve pancreatitis induced by pancreatin^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

615.76

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156177-65-0

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C[C@]12N3C4=C(C5=CC(CSCC)=CC=C53)C(CNC6=O)=C6C(C7=C8)=C4N([C@@H](C[C@]2(O)C(OC)=O)O1)C7=CC=C8CSCC

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• [1]. Saporito MS, Hudkins RL, Maroney AC. Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases. Prog Med Chem. 2002;40:23-62.  [Content Brief]

  [2]. Maroney AC, Finn JP, Connors TJ, et al. Cep-1347 (KT7515), a semisynthetic inhibitor of the mixed lineage kinase family. J Biol Chem. 2001;276(27):25302-25308.  [Content Brief]

  [3]. Mitobe Y, Nakagawa-Saito Y, Togashi K, et al. CEP-1347 Targets MDM4 Protein Expression to Activate p53 and Inhibit the Growth of Glioma Cells. Anticancer Res. 2022;42(10):4727-4733.  [Content Brief]

  [4]. Mitobe Y, Suzuki S, Nakagawa-Saito Y, et al. The Novel MDM4 Inhibitor CEP-1347 Activates the p53 Pathway and Blocks Malignant Meningioma Growth In Vitro and In Vivo. Biomedicines. 2023;11(7):1967.  [Content Brief]

  [5]. Maroney AC, et al. Motoneuron apoptosis is blocked by CEP-1347 (KT 7515), a novel inhibitor of the JNK signaling pathway. J Neurosci. 1998;18(1):104-111.  [Content Brief]

  [6]. Wagner AC, et al. EP-1347 inhibits caerulein-induced rat pancreatic JNK activation and ameliorates caerulein pancreatitis. Am J Physiol Gastrointest Liver Physiol. 2000;278(1):G165-G172.  [Content Brief]