Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group

Viallet, Jean; Shepherd, F.; Ayoub, Joseph; Cormier, Yvon; DiPietro, Natalie A.; Steward, W.P.

doi:10.1016/0169-5002(95)00600-1

Cited by 23 publications

(12 citation statements)

References 7 publications

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“…187 However, since its clinical evaluation showed severe myelotoxicity that probably impaired the reaching of effective therapeutic doses, and its phase II clinical development was discontinued. 188,189 Whereas BAM alkylates and cross-links in the major groove of DNA, its attachment to the polypyrrolic frame of distamycin A produces high preference for monoalkylation of 3 0 -adenine-N3 atom located in the sequence 5 0 -TTTTGA-3 0 in the minor groove of DNA, 190 with no evidence of guanine-N7 alkylation, which is characteristic of conventional nitrogen mustards such as melphalan or chlorambucil. It is remarkable that the cytotoxicity can be improved by increasing the number of pyrrole residues from three of the tallimustine to four in the compound 122 and a relationship has been demonstrated between the number of pyrroles and citotoxicity.…”

Section: B Benzoic Acid Mustard Distamycin Derivativesmentioning

confidence: 98%

DNA minor groove binders as potential antitumor and antimicrobial agents

Baraldi

Bovero

Fruttarolo

et al. 2004

Medicinal Research Reviews

359

222

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DNA minor groove binders constitute an important class of derivatives in anticancer therapy. Some of these compounds form noncovalent complexes with DNA (e.g., distamycin A, Hoechst 33258, and pentamidine) while others DNA-binding compounds (such as CC-1065) cause cleavages in the DNA backbone. In this article, we have reviewed the minor groove binders currently in preclinical evaluation in the last years. Diarylamidines such as DAPI, berenil, and pentamidine; bis-benzimidazoles such as Hoechst 33258; ecteinascidins, pyrrololo [2,1-c]-[1,4]-benzodiazepines (PBDs), CC-1065, and distamycins are the classes discussed in this review article. A special section has been dedicated to hybrid molecules resulted by the combination of two minor groove binders, especially for derivatives of naturally occurring antitumor agents, such as anthramycin or the alkylating unit of the antibiotic CC-1065, and distamycin frames.

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Section: B Benzoic Acid Mustard Distamycin Derivativesmentioning

confidence: 98%

DNA minor groove binders as potential antitumor and antimicrobial agents

Baraldi

Bovero

Fruttarolo

et al. 2004

Medicinal Research Reviews

359

222

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“…9,10 Development of tallimustine was promising as phase I and II clinical trials demonstrating significant antitumor, but notably myelotoxicity led to the phase II clinical development being halted. 11,12,13 As a class of compounds, S-MGBs are not inherently cytotoxic: structural alterations away from that of distamycin led to anti-infective compounds with favourable selectivity indices. 14 Despite the lack of class specific toxicity, some S-MGBs inhibit the growth of lung cancer cells.…”

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confidence: 99%

An evaluation of Minor Groove Binders as anti-lung cancer therapeutics

Scott

Puig-Sellart

Khalaf

et al. 2016

Bioorganic & Medicinal Chemistry Letters

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A series of 47 structurally diverse MGBs, derived from the natural product distamycin, was evaluated for anti-lung cancer activity by screening against the melanoma cancer cell line B16-F10. Five compounds have been found to possess significant activity, more so than a standard therapy, Gemcitabine. Moreover, one compound has been found to have an activity around 70-fold that of Gemcitabine and has a favourable selectivity index of greater than 125. Furthermore, initial studies have revealed this compound to be metabolically stable and thus it represents a lead for further optimisation towards a novel treatment for lung cancer.

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“…Clinical trials to date with several, mainly A.T selective compounds have been somewhat disappointing [68,69], but recent improvements in sequence selectivity and understanding of the biological mechanisms of action predicts an exciting time ahead in rational drug design and clinical application.…”

Section: Discussionmentioning

confidence: 99%

The Genome as a Drug Target Sequence Specific Minor Groove Binding Ligands

Turner¹,

Denny

2000

CDT

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The ability to target defined sequences on the DNA molecule would be of enormous benefit to the treatment of human disease. Towards this goal much research has been invested in examining the DNA binding and biological mechanisms of action of sequence selective minor groove binding ligands. These compounds act in a variety of ways to inhibit gene expression and DNA replication and also alter nuclear architecture. Concomitant with this, minor groove adducts formed by certain compounds are inefficiently removed by cellular DNA repair systems and are extremely cytotoxic. Additionally compounds targeting A.T rich DNA sequences have found clinical use in the treatment of particular parasitic infections.

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Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group

Cited by 23 publications

References 7 publications

DNA minor groove binders as potential antitumor and antimicrobial agents

DNA minor groove binders as potential antitumor and antimicrobial agents

An evaluation of Minor Groove Binders as anti-lung cancer therapeutics

The Genome as a Drug Target Sequence Specific Minor Groove Binding Ligands

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