Bendamustine hydrochloride (EP-3101) (IC50 of 50 μM) is an alkylating agent associated with DNA damage.

DNA damage:50 μM

Bendamustine具有明显的活性,单独用25 mg/kg 作用于3种肿瘤细胞 (DoHH-2, Granta 519 和RAMOS).Bendamustine 抑制Granta 519 和RAMOS生长(%TGI分别为74% 和 81%),在Granta 519(%TGD 为124%) 上的作用效果比DoHH-2或RAMOS(分别为69%和43%)高.DoHH-2最敏感,ORR为30%,且抑制69%肿瘤生长.

Bendamustine比环磷酰胺, Cisplatinum, 或卡莫司汀造成的DNA单链和双链断裂更广泛也更有效。Bendamustine抑制有丝分裂检测点,造成有丝分裂发生巨大突变。Bendamustine 调节凋亡、 DNA修复和有丝分裂检测到涉及的基因。Bendamustine与等摩尔剂量的 Lomustine相比,具有非常低的致畸效果。Bendamustine处理的 MCF-7/ADR细胞后,26%显示微核化,而DMSO处理的细胞中只有6%。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。 Bendamustine 处理SU-DHL-9细胞,导致这些基因中的全部3个（polo样激酶1 , Aurora 激酶 A和cyclin B1）的mRNA表达下调60% 到80%。Bendamustine 作用于非Hodgkin's 淋巴细胞,与其他烷化剂相比能够独特调节DNA 修复通路。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。

SU-DHL-1 and SU-DHL-9 cells are preincubated for 30 minutes with either 6 mM methoxyamine or 50 μM O6-benzylguanine, inhibitors of Ape-1 base excision repair enzyme, or alkylguanyl transferase enzyme, respectively. The cells are then exposed to various concentrations of Bendamustine for 72 hours. Cytotoxicity is evaluated by the MTT viability assay and an IC50 is determined as the drug concentration that inhibited by 50% the viability value of the untreated control. Analyses are done.(Only for Reference)