基本信息

产品描述

Bendamustine HCL是一种DNA损伤剂，无细胞试验中IC50为50 μM。

靶点（IC50 & Targe）

DNA synthesis

体外研究

Bendamustine造成的DNA单链和双链断裂比Cyclophosphamide, Cisplatinum, 或 Carmustine造成的更广泛也更稳定。Bendamustine 特定转录和转录后调节凋亡, DNA修复,和有丝分裂检测到涉及的基因。Bendamustine 作用于非Hodgkin's 淋巴细胞，与其他烷化剂相比，独特调节DNA 修复通路。Bendamustine抑制有丝分裂检测点，造成有丝分裂发生巨大突变。Bendamustine 处理SU-DHL-9细胞，导致这些基因中的全部三个polo样激酶1 (PLK-1), Aurora 激酶 A, 和cyclin B1的mRNA表达下调60% 到80%。Bendamustine处理的 MCF-7/ADR细胞中26%显示微核化，而DMSO处理的细胞中只有6%。[1]使用浓度为1 μg/mL 到50 μg/mL的 Bendamustine 单独处理，48小时后，观察到毒性为30.4%到94.8%，这种作用存在剂量和时间依赖性。未处理和预处理的 CLL 细胞的LD50分别为7.3 或 4.4 μg /mL。[3] 髓细胞和乳腺癌细胞抗 Bendamustine，但是HL-60细胞对Bendamustine 具有适中的敏感度。与等摩尔剂量的 Lomustine相比，Bendamustine具有非常低的致畸效果。[4]

体内研究

Bendamustine 按25 mg/kg剂量单独作用于三种肿瘤细胞 (DoHH-2, Granta 519 和RAMOS)，具有显著的活性。DoHH-2最敏感，ORR为30%，且抑制69%肿瘤生长。 Bendamustine 抑制Granta 519 和RAMOS生长(%TGI分别为74% 和 81%), 作用于Granta 519(%TGD 为124%) 效果比作用于DoHH-2或RAMOS(分别为69%和43%)高。[5]

细胞实验

Cell lines: SU-DHL-1 和 SU-DHL-9 细胞

Concentrations: 0 μM -100 μM

Incubation Time: 72 小时

Method: SU-DHL-1和SU-DHL-9细胞与6 mM Methoxyamine 或 50 μM O6-benzylguanine预温育30分钟，Methoxyamine 与 O6-benzylguanine分别是Ape-1碱基切除修复酶抑制剂，和烷脒基转移酶抑制剂。使用不同浓度Bendamustine处理细胞72小时。通过MTT活性检测评估细胞毒性，且测定IC50值，进行分析。

(Only for Reference)

动物实验

Animal Models: 携带DoHH-2, Granta 519 的C.B.-17 scid小鼠，携带 SuDHL-4, RAMOS的C.B.-17 scid-bg小鼠

Formulation: Control

Dosages: 25 mg/kg

Administration: 静脉注射

(Only for Reference)

参考文献

[1] Leoni LM, et al. Clin Cancer Res. 2008, 14(1), 309-317.

[2] Schw?nen C, et al. Leukemia. 2002, 16(10), 2096-2105.

[3] Konstantinov SM, et al. J Cancer Res Clin Oncol. 2002, 128(5), 271-278.

[4] Ackler S, et al. Br J Pharmacol. 2012.

[5] Chow KU, et al. Biochem Pharmacol. 2003, 66(5), 711-724.

安全信息

图形或危害标志
提示语	Danger
危险说明	H301 H351 H360
防范说明	P201 P202 P264 P270 P281 P301+P310 P308+P313 P321 P330 P405 P501
UN号码	2811
危险分类	6.1
包装等级	III
WGK	3
RTECS	DE1590000

基本信息

安全信息

图形或危害标志
危险性说明	H301: Toxic if swallowed. H315: Causes skin irritation. H319: Causes serious eye irritation. H335: May cause respiratory irritation. H341: Suspected of causing genetic defects .. H351: Suspected of causing cancer .. H371: May cause damage to organs Bone Marrow. H361fd: Reproductive toxicity
防范说明	P201: Obtain special instructions before use. P202: Do not handle until all safety precautions have been read and understood. P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing P264: Wash hands thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P281: Use personal protective equipment as required. P301 + P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: . P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P308 + P313: IF exposed or concerned: Get medical advice/ attention. P309: IF exposed or if you feel unwell: . P309 + P311: IF exposed or if you feel unwell: Call a POISON CENTER or doctor/physician. P311: Call a POISON CENTER or doctor/physician. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P321: Specific treatment (see . on this label). P330: Rinse mouth. P332 + P313: If skin irritation occurs: Get medical advice/ attention. P337 + P313: If eye irritation persists: Get medical advice/attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P362: Take off contaminated clothing and wash before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to local regulations.