Amsacrine lactate  (Synonyms: m-AMSA lactate; Acridinyl anisidide lactate)

Amsacrine lactate (m-AMSA lactate) is a Topoisomerase II inhibitor. Amsacrine lactate intercalates into DNA. Amsacrine lactate induces Ca²⁺-mediated inactivation of ERK, and also downregulates AKT, promoting MCL1 downregulation mediated by GSK3β via reducing the phosphorylation level of GSK3β. Amsacrine lactate induces Apoptosis by activating Caspase-9 and Caspase-3. Amsacrine lactate blocks HERG potassium channels in the open/inactivated state. Amsacrine lactate induces chromosomal aberrations and sister chromatid exchanges, and inhibits the synthesis of RNA and DNA. Amsacrine lactate exhibits anti-leukemic activity. Amsacrine lactate causes cardiac repolarization disorders, QT interval prolongation, ventricular arrhythmias, and increases the risk of sudden cardiac death. Amsacrine lactate can be used in research related to acute myeloid leukemia, lymphoma and progressive malignancies^[1][2][3][4].

Amsacrine (1 μM; 4 h) lactate induces downregulation of phosphorylated and total AKT in acute myeloid leukemia U937 cells via a proteasome-dependent pathway, and this effect is abolished by pretreatment with MG132 (5 μM; 1 h)^[1].
Amsacrine (0.01-100 μM) lactate potently blocks wild-type HERG potassium channels heterologously expressed in Xenopus oocytes, with an IC₅₀ of 2.0 μM, and exhibits partial reversibility after washout^[2].
The inhibitory effect of Amsacrine (10 μM) lactate on HERG potassium channels heterologously expressed in Xenopus oocytes is attenuated in the HERG^Y652A mutant, and completely abolished in the HERG^F656A and HERG^Y652A/F656A mutants, indicating that this effect depends on the aromatic residues in the S6 segment of the pore region^[2].
Lactate salt of Amsacrine (at different concentrations; perfused to achieve steady-state block) potently blocks wild-type HERG potassium channels stably expressed in 293 cells, with an IC₅₀ of 209.4 nM^[2].
Amsacrine lactate induces chromosome aberrations, sister chromatid exchanges and micronucleus formation in vitro in a variety of mammalian cells^[3].
Amsacrine (0.005-0.25 μg/mL) lactate induces a dose-dependent increase in chromosome aberrations and sister chromatid exchanges in cultured normal peripheral blood lymphocytes in vitro, with 0.005 μg/mL increasing SCE by 1.5-fold and 0.25 μg/mL increasing SCE by 12-fold^[4].
Amsacrine (5.0 μg/mL; 36 h) lactate inhibits 80% of RNA synthesis and 60% of DNA synthesis in cultured human peripheral blood lymphocytes in vitro, and exerts no significant effect on protein synthesis after 36 h of incubation^[4].

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

Amsacrine (0.5-12 mg/kg; i.p.; single administration) lactate exerts significant genotoxicity on mouse bone marrow at doses of 9 and 12 mg/kg, which is mainly characterized by clastogenic effects, along with weak aneuploidy-inducing activity; it also causes dose-dependent inhibition of erythroblast proliferation at these higher doses^[3].

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

483.54

C₂₄H₂₅N₃O₆S

80277-11-8

O=C(C(C)O)O.O=S(NC1=CC=C(C(OC)=C1)NC2=C3C=CC=CC3=NC4=C2C=CC=C4)(C)=O

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Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. 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 : an international journal on programmed cell death. 2017 Mar;22(3):406-420.  [Content Brief]

  [2]. Thomas D, et al. Inhibition of cardiac HERG currents by the DNA topoisomerase II inhibitor amsacrine: mode of action. British journal of pharmacology. 2004 Jun;142(3):485-94.  [Content Brief]

  [3]. Attia SM. Molecular cytogenetic evaluation of the mechanism of genotoxic potential of amsacrine and nocodazole in mouse bone marrow cells. Journal of applied toxicology : JAT. 2013 Jun;33(6):426-33.  [Content Brief]

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