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ID: ALA3399924

Journal: Bioorg Med Chem Lett

Title: Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent.

Authors: Ichimaru Y, Saito H, Uchiyama T, Metori K, Tabata K, Suzuki T, Miyairi S.

Abstract: Indirubin is a potent inhibitor of cell cycle-related protein kinases by binding to the ATP-binding site and thus is a promising compound for development as an antitumor drug. We prepared indirubin 3'-(O-oxiran-2-ylmethyl)oxime (Epox/Ind), in which the ATP-binding site orientated part was attached by non-specific alkylating group. The IC50 value of Epox/Ind at 1.7 μM in HepG2 cells is comparable to that of cisplatin (4.0 μM). Furthermore, Epox/Ind was shown to be metabolized by a HepG2 cell lysate into indirubin 3'-(O-2,3-dihydroxypropyl)oxime (E804), the sole extractable metabolite. The lower toxicity of this metabolite may explain the lack of cytotoxicity of 1 μM Epox/Ind observed in HepG2 cells beyond an initial loss of viability in the first 24h of treatment.

CiteXplore: 25765906

DOI: 10.1016/j.bmcl.2015.02.053