Amsacrine  (Synonyms: m-AMSA; acridinyl anisidide)

Amsacrine (m-AMSA; acridinyl anisidide) is an inhibitor of topoisomerase II, and acts as an antineoplastic agent which can intercalates into the DNA of tumor cells.

Amsacrine (m-AMSA) 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 (m-AMSA) causes a negative shift in the voltage dependence of both activation (?7.6 mV) and inactivation (?7.6 mV). HERG current block by amsacrine is not frequency dependent^[1]. In vitro studies of normal human lymphocytes with various concentrations of Amsacrine (m-AMSA), 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)^[3]. Amsacrine (m-AMSA)-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 (m-AMSA) induces MCL1 down-regulation by decreasing its stability. Further, amsacrine-treated U937 cells show AKT degradation and Ca²⁺-mediated ERK inactivation^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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 (m-AMSA) 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^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

393.46

C₂₁H₁₉N₃O₃S

51264-14-3

Solid

Orange to red

CS(=O)(NC1=CC=C(NC2=C(C=CC=C3)C3=NC4=CC=CC=C42)C(OC)=C1)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

• [1]. Thomas D, et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. Br J Pharmacol. 2004 Jun;142(3):485-94.  [Content Brief]

  [2]. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. J Appl Toxicol. 2013 Jun;33(6):426-33.  [Content Brief]

  [3]. Kao-Shan CS, et al. Cytogenetic effects of amsacrine on human lymphocytes in vivo and in vitro. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):989-97.  [Content Brief]

  [4]. Lee YC, et al. Amsacrine-induced apoptosis of human leukemia U937 cells is mediated by the inhibition of AKT- and ERK-induced stabilization of MCL1. Apoptosis. 2016 Oct 19  [Content Brief]