New antitumor antibiotics, duocarmycins B1 and B2.

Ogawa, Tatsuhiro; Ichimura, Michio; Katsumata, Shigeo; Morimoto, Makoto; Takahashi, Keiichi

doi:10.7164/antibiotics.42.1299

Cited by 56 publications

(11 citation statements)

References 4 publications

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“…[1] Conventional agentsh ave been appliedt om any cancer therapies, and new antitumor agents having therapeutic potentialare being discovered. Duocarmycin, first reported in 1988 [2,3] and its analoguesh ave been beneficial in treating many types of tumor disease [1,4] through covalenti nteraction with aD NA minor-groovea denine N3 alkylation site. [5,6] However,i ne ukaryotic cells, the assembly of DNA and histone proteins into nucleosomes (the basic repeating subunits of chromatin) packs over two meters of DNA into the confines of the nucleus.…”

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confidence: 99%

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA

Zou

Kizaki

Pandian

et al. 2016

Chemistry A European J

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To evaluate the reactivity of antitumor agents in a nucleosome architecture, we conducted in vitro studies to assess the alkylation level of duocarmycin B2 on nucleosomes with core and linker DNA using sequencing gel electrophoresis. Our results suggested that the alkylating efficiencies of duocarmycin B2 were significantly decreased in core DNA and increased at the histone-free linker DNA sites when compared with naked DNA conditions. Our finding that nucleosome assembly alters the accessibility of duocarmycin B2 to duplex DNA could advance its design as an antitumor agent.

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confidence: 99%

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA

Zou

Kizaki

Pandian

et al. 2016

Chemistry A European J

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“…[3][4][5][6] The DUM's antitumor activity occurs through a sequencespecific covalent binding to the minor groove of DNA, which in turn leads to DNA fragmentation. [7,8] This DNA binding activity appears to be similar to that seen with other minor groove-binding agents including CC-1065 and its analogues.…”

Section: Introductionmentioning

confidence: 99%

Use of KW-2189, a DNA Minor Groove-Binding Agent, in Patients with Hepatocellular Carcinoma: A North Central Cancer Treatment Group (NCCTG) Phase II Clinical Trial

Alberts

Suman

Pitot

et al. 2007

J Gastrointest Canc

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“…The exceptionally potent antitumour antibiotics CC-1065 (1) [1][2][3][4] and duocarmycins (2 -3) [5][6][7][8][9][10][11][12][13][14] represent a class of natural compounds, that derive their biological effects through the reversible, stereoelectronicallycontrolled sequence selective alkylation of DNA [15][16][17][18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

CC-1065 and the duocarmycins: recent developments

Cacciari

Romagnoli

Baraldi

et al. 2000

Expert Opinion on Therapeutic Patents

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It is accepted that neoplastic diseases are related to gene alteration or oncogene activation. In particular, DNA minor groove binding drugs have been extensively studied through the years in order to influence the regulation of gene expression by means of specific interactions with DNA based moieties. In this field, analogues of naturally occurring antitumour agents, such as CC-1065 and/or the duocarmycins, represent a new class of highly potent antineoplastic compounds, currently under investigation. CC-1065 and duocarmycins represent a class of exceptionally potent antitumour antibiotics that derive their biological effects from the reversible, stereoelectronically-controlled sequence selective alkylation of DNA. All natural compounds showed a cytotoxicity against leukaemia L1210 cell lines in the range 10 -220pM but while CC-1065 showed a good antitumour activity in an in vivo model (optimal dose from 10 -100 µg/g), duocarmycins showed weak antitumour activity. Despite its potency, CC-1065 cannot be used in humans due to eventual fatality. For this reason many scientists have focused their attention on this class of compounds, in order to obtain new derivatives with equal in vitro potency but a better profile in in vivo models. This effect is accompanied by dramatic changes in the morphology of hepatic mitochondria. On this basis, the recent developments on SARs for this class of compounds and their possible use as therapeutic agents are reviewed, with particular emphasis on recent patent literature and, finally, a conclusive opinion will be given on this topic.

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New antitumor antibiotics, duocarmycins B1 and B2.

Cited by 56 publications

References 4 publications

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA

Use of KW-2189, a DNA Minor Groove-Binding Agent, in Patients with Hepatocellular Carcinoma: A North Central Cancer Treatment Group (NCCTG) Phase II Clinical Trial

CC-1065 and the duocarmycins: recent developments

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New antitumor antibiotics, duocarmycins B1 and B2.

Cited by 56 publications

References 4 publications

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B2 to Duplex DNA

Use of KW-2189, a DNA Minor Groove-Binding Agent, in Patients with Hepatocellular Carcinoma: A North Central Cancer Treatment Group (NCCTG) Phase II Clinical Trial

CC-1065 and the duocarmycins: recent developments

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Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA

Nucleosome Assembly Alters the Accessibility of the Antitumor Agent Duocarmycin B₂ to Duplex DNA