生物活性

• 描述Ribonucleotide reductase catalyzes the formation of deoxyribonucleotides from ribonucleotides, which is essential for maintaining a balanced pool of deoxyribonucleotides for DNA synthesis and repair. Triapine is a potent inhibitor of ribonucleotide reductase. In vitro, it fully blocked ischemic neurotoxicity at 0.5 μM with an EC₅₀ value of 0.35 μM. It also inhibited hypoxic toxicity with an EC₅₀ value of around 0.75 μM. Triapine at 0.63 μM and 0.45 μM completely inhibited HGH-induced mitochondrial dysfunction and LDH release with EC₅₀ values of 0.2 - 0.35 μM. In neuron cells, treatment with 10 μM Triapine decreased 100 μM glutamate-induced cell death by 89%. In cortical neurons, the addition of 10 μM Triapine 24h prior to and during the experiment reduced neurotoxicity of 1 μM staurosporine by 47%Jiang ZG, Lebowitz MS, Ghanbari HA. Neuroprotective activity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811), a cancer therapeutic agent. CNS Drug Rev. 2006 Spring;12(1):77-90. doi: 10.1111/j.1527-3458.2006.00077.x. PMID: 16834759; PMCID: PMC6741723.https://pubmed.ncbi.nlm.nih.gov/16834759/. In mice bearing M109 lung carcinoma, intravenous injection of triapine either once daily (24 mg/kg) or twice daily (6 mg/kg) for 5 consecutive days significantly inhibited the tumor growth. The administration of triapine (5 mg/kg, twice daily, 5 consecutive days) also inhibited the DNA synthesis in the bone marrow and intestinal mucosa^[5].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HCT116 cells	4 μM	Function assay	24 h	Induction of ROS generation in human HCT116 cells expressing wild type p53 at 4 uM after 24 hrs by spectrophotometry	24900837
  human HCT116 cells	-	Cytotoxicity assay	96 h	Dark cytotoxicity against human HCT116 cells expressing wild type p53 after 96 hrs by MTT assay, IC50=1.226 μM	24900837
  KB-3-1 cells	-	Cytotoxicity assay	72 h	Cytotoxicity against human P-gp-negative KB-3-1 cells after 72 hrs by MTT assay, IC50=1.4 μM	19397322

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• 动物研究
  剂量	Mice: 10 mg/kg[3] (i.p.); 20 mg/kg[4] (s.c.)
  给药途径	i.p., s.c.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02644122	-	-	Terminated(Slow enrollment)	-	-
  NCT02644122	Metastatic Squamous Neck Cance... more >>r With Occult Primary Squamous Cell Carcinoma Collapse <<	Phase 2	Terminated(Slow enrollment)	-	United States, California ... more >> UC San Diego Moores Cancer Center La Jolla, California, United States, 92093 Collapse <<
  NCT00024323	Unspecified Adult Solid Tumor,... more >> Protocol Specific Collapse <<	Phase 1	Completed	-	United States, Arizona ... more >> Arizona Clinical Research Center Tucson, Arizona, United States, 85712 United States, Connecticut Yale Comprehensive Cancer Center New Haven, Connecticut, United States, 06520-8028 Collapse <<

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• 参考文献

• [1] Jiang ZG, Lebowitz MS, Ghanbari HA. Neuroprotective activity of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (PAN-811), a cancer therapeutic agent. CNS Drug Rev. 2006 Spring;12(1):77-90.

  [2] Finch RA, Liu M, et al. Triapine (3-aminopyridine-2-carboxaldehyde- thiosemicarbazone): A potent inhibitor of ribonucleotide reductase activity with broad spectrum antitumor activity. Biochem Pharmacol. 2000 Apr 15;59(8):983-91.

  [3] Lin ZP, Zhu YL, et al. Combination of triapine, olaparib, and cediranib suppresses progression of BRCA-wild type and PARP inhibitor-resistant epithelial ovarian cancer. PLoS One. 2018 Nov 16;13(11):e0207399.

  [4] Dai L, Chen J, et al. Ribonucleotide Reductase Inhibitor 3-AP Induces Oncogenic Virus Infected Cell Death and Represses Tumor Growth. J Cancer. 2018 Oct 31;9(23):4503-4509.

  [5] 10692563

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