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 (KT7515) (0-500 nM；3 天) 在具有野生型 p53 的恶性脑膜瘤细胞中降低 MDM4 的表达并激活 p53 通路^[4]。
CEP-1347 在缺乏营养因子的大鼠胚胎运动神经元中通过抑制 JNK1 的活性来促进运动神经元的存活。CEP-1347 对 JNK1 激活的 IC₅₀ 值与运动神经元存活的 EC₅₀ 值均为 20 nM^[5]。
CEP-1347 (0.2-20 μM; 2 小时) 在分离的胰腺腺泡中能剂量依赖性地抑制了胰脏素诱导的 JNK 激活，2 μM 时几乎完全抑制^[6]。

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

CEP-1347 (0-60 mg/kg; 皮下注射) 在 Caerulein (HY-A0190) (10 μg/kg; 静脉注射) 处理的大鼠中能够剂量依赖性地抑制 Caerulein 诱导的 JNK 的激活，并改善胰脏素诱导的胰腺炎^[6]。

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

615.76

C₃₃H₃₃N₃O₅S₂

156177-65-0

固体

White to off-white

Room temperature in continental US; may vary elsewhere.

• [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]