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Amsacrine hydrochloride

CAS No. : 54301-15-4

MCE 站：Amsacrine hydrochloride

产品活性：Amsacrine hydrochloride (m-AMSA hydrochloride; acridinyl anisidide hydrochloride) 是肿瘤细胞 DNA 嵌入剂，还能抑制拓扑异构酶 II。

研究领域：Cell Cycle/DNA Damage  |  Autophagy

作用靶点：Topoisomerase  |  Autophagy

In Vitro: Amsacrine (mAMSA) blocks HERG currents in HEK 293 cells and Xenopus oocytes in a concentration-dependent manner, with IC₅₀ values of 209.4 nM and 2.0 μM, respectively. Amsacrine (mAMSA) causes a negative shift in the voltage dependence of both activation (?7.6 mV) and inactivation (?7.6 mV). HERG current block by Amsacrine (mAMSA) is not frequency dependent. In vitro studies of normal human lymphocytes with various concentrations of Amsacrine (mAMSA), show both increased levels of chromosomal aberrations, ranging from 8% to 100%, and increase SCEs, ranging from 1.5 times the normal at the lowest concentration studied (0.005 μg/mL) to 12 times the normal (0.25 μg/mL). Amsacrine (mAMSA)-induced apoptosis of U937 cells is characterized by caspase-9 and caspase-3 activation, increased intracellular Ca²⁺ concentration, mitochondrial depolarization, and MCL1 down-regulation. Amsacrine induces MCL1 down-regulation by decreasing its stability. Further, amsacrine-treated U937 cells show AKT degradation and Ca²⁺-mediated ERK inactivation.

In Vivo: In animals treated with different doses of amsacrine (0.5-12 mg/kg), the frequencies of micronucleated polychromatic erythrocytes increase significantly after treatment with 9 and 12 mg/kg. Furthermore, the present study demonstrates for the first time that Amsacrine (mAMSA) has high incidences of clastogenicity and low incidences of aneugenicity whereas nocodazole has high incidences of aneugenicity and low incidences of clastogenicity during mitotic phases in vivo.

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