生物活性 | |||
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描述 | DNA damage is an abnormal chemical structure in DNA, while a mutation is a change in the sequence of standard base pairs. DNA damages cause changes in the structure of the genetic material and prevent the replication mechanism from functioning and performing properly. Temozolomide is converted to the active metabolite 5-(3-methyltriazen-1-yl) imidazole-4-carboxamide (MTIC) by non-enzymatic chemical conversion that produces DNA damage[3]. In vitro, temozolomide exhibited anti-proliferation to human malignant glioma cell lines U373MG, U87MG, and T98G with IC50 values of 40, 30 and 350 μM, respectively. Temozolomide induced apoptosis in the MGMT expressing cells occurred through AKT-Glycogen-Synthase-Kinase-3β signaling and is mediated by myelocytomatosis oncoprotein[4]. Temozolomide treatment at concentration of 100 mM for 72h increased the population at the G2/M phase and decreased the population at the G1 phase in all malignant glioma cells. In addition, temozolomide induced autophagy in U373-MG cells[5]. In vivo, administration of 40 mg/kg temozolomide significantly increased survival times in a B16F10 mouse metastatic melanoma model[6]. Treatment with temozolomide at dose of 2.5 mg/kg daily for 4 weeks resulted in a 78.30% tumor suppression, and reduced microvessel density in the glioblastoma orthotopic xenograft model[7]. |
细胞研究 | |||||
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细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
A172 | 200 μM | Function Assay | 48 h | increases BRCC3 mRNA expression | 25337721 |
A172 | 200 μM | Function Assay | 48 h | increases the expression of BRCA1, BRCA2, RAD51 and FANCD2 | 25337721 |
A172 | 200 μM | Function Assay | 24/72/120 h | increases γH2AX foci formation time-dependently | 25337721 |
临床研究 | |||||
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NCT号 | 适应症或疾病 | 临床期 | 招募状态 | 预计完成时间 | 地点 |
NCT00611247 | Leukemia, Myeloid | Phase 2 | Completed | - | United States, California ... 展开 >> Stanford University School of Medicine Stanford, California, United States, 94305 收起 << |
NCT00611247 | - | Completed | - | - | |
NCT00869050 | Neuroendocrine Tumors | Phase 2 | Completed | - | United States, New York ... 展开 >> Columbia University Medical Center New York, New York, United States, 10032 收起 << |
实验方案 | |||
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1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
5.15mL 1.03mL 0.52mL |
25.75mL 5.15mL 2.58mL |
51.51mL 10.30mL 5.15mL |
参考文献 |
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