title: Indirubin 3'-(O-oxiran-2-ylmethyl)oxime: a novel anticancer agent.
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.
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ichimaru
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Saito
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Taketo
authors.initials: T
authors.lastname: Uchiyama
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Metori
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tabata
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. Electronic address: miyairi.shinichi@nihon-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyairi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D010091:Oximes; C000603597:indirubin 3'-(O-oxiran-2-ylmethyl)oxime
keywords: Adduct; Anticancer agent; Epoxide; Indirubin; Metabolism