Merbarone (NSC 336628) is an orally active inhibitor of topoisomerase II. Merbarone acts primarily by blocking topoisomerase II-mediated DNA cleavage without stabilizing topo II-DNA covalent complexes. Merbarone is an anticancer agent[1][2][4].
Merbarone (1-100 µM) inhibits L1210 cells proliferation in a concentration-dependent manner, with an IC50 of 10 µM[3].Merbarone (10-200 µM; 10 min) inhibits DNA relaxation catalyzed by human topoisomerase IIα, with an IC50 of ∼40 µM[1].Merbarone (25-200 µM; 6 min) blocks tyopoisomerase II-mediated DNA cleavage, with an IC50 of ∼50 µM[1].Merbarone (100 µM; 6 min) inhibits topoisomerase II-mediated DNA cleavage in a global manner[1].Merbarone (100 µM; 6 min) does not impair topoisomerase II•DNA binding[1].Merbarone (200 µM; 4-16 min) does not inhibit topoisomerase II-catalyzed ATP hydrolysis[1].
Merbarone (50 mg/kg; daily i.p. for 5 d) achieves a maximum increased life span (ILS) of 101% in P388 murine leukemia[2].Merbarone (124 mg/kg; daily p.o. for 9 d) has anti-tumor activity in mice[2].
References:
[1]. Fortune JM, et, al. Merbarone inhibits the catalytic activity of human topoisomerase IIalpha by blocking DNA cleavage. J Biol Chem. 1998 Jul 10;273(28):17643-50.
[2]. Brewer AD, et, al. 5-(N-phenylcarboxamido)-2-thiobarbituric acid (NSC 336628), a novel potential antitumor agent. Biochem Pharmacol. 1985 Jun 1;34(11):2047-50.
[3]. Cooney DA, et, al. Initial mechanistic studies with merbarone (NSC 336628). Biochem Pharmacol. 1985 Sep 15;34(18):3395-8.
[4]. Chen M, et, al. Differences in inhibition of chromosome separation and G2 arrest by DNA topoisomerase II inhibitors merbarone and VM-26. Cancer Res. 1995 Apr 1;55(7):1509-16.