Topoisomerase I Inhibitors: Chemical Biology

Teicher, Beverly A.

doi:10.1007/978-1-4614-0323-4_10

Cited by 2 publications

(4 citation statements)

References 119 publications

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“…The wide range of in vivo tumor models like syngeneic, human tumor xenograft, orthotopic, metastatic, and genetically engineered mouse models is available from the basis of the compounds selected and treatments that go into clinical testing of patients [ 55 ]. The ability to exhibit anchorage-independent cell growth (colony-forming capacity in semisolid media) has been considered to be fundamental in cancer biology because it has been connected with tumor cell aggressiveness in vivo such as tumorigenic and metastatic potentials and also utilized as a marker for in vitro transformation.…”

Section: Anchorage-independent Tumor Model Systemmentioning

confidence: 99%

Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Rajeswari

Kapoor²,

Sistla³

et al. 2012

International Journal of Cell Biology

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Cancer progression is a multistep process during which normal cells exhibit molecular changes that culminate into the highly malignant and metastatic phenotype, observed in cancerous tissues. The initiation of cell transformation is generally associated with genetic alterations in normal cells that lead to the loss of intercellular- and/or extracellular-matrix- (ECM-) mediated cell adhesion. Transformed cells undergo rapid multiplication and generate more modifications in adhesion and motility-related molecules which allow them to escape from the original site and acquire invasive characteristics. Integrins, which are multifunctional adhesion receptors, and are present, on normal as well as transformed cells, assist the cells undergoing tumor progression in creating the appropriate environment for their survival, growth, and invasion. In this paper, we have briefly discussed the role of ECM proteins and integrins during cancer progression and described some unique conditions where adhesion-related changes could induce genetic mutations in anchorage-independent tumor model systems.

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Section: Anchorage-independent Tumor Model Systemmentioning

confidence: 99%

Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Rajeswari

Kapoor²,

Sistla³

et al. 2012

International Journal of Cell Biology

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Section: Introductionmentioning

confidence: 99%

“…Out of hundreds of biologically evaluated indenoisoquinolines, indotecan (LMP400, 4 ) and indimitecan (LMP776, 5 ) were promoted to a Phase I clinical trial at the National Institutes of Health, which began in 2010 . Likewise, the indolocarbazole class is a potential source of therapeutic Top1 inhibitors with advantages similar to the indenoisoquinoline class . One exemplary indolocarbazole, the Top1 inhibitor edotecarin ( 7 ), advanced to a Phase III clinical trial, where it unfortunately failed …”

Section: Introductionmentioning

confidence: 99%

“…13 Likewise, the indolocarbazole class is a potential source of therapeutic Top1 inhibitors with advantages similar to the indenoisoquinoline class. 14 One exemplary indolocarbazole, the Top1 inhibitor edotecarin (7), advanced to a Phase III clinical trial, where it unfortunately failed. 15 Previous studies of indenoisoquinoline glycosides were inspired by the possibility that "platform hopping" carbohydrates from indolocarbazoles to indenoisoquinolines might yield potent, novel Top1 poisons.…”

Section: ■ Introductionmentioning

confidence: 99%

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Synthesis and Biological Evaluation of New Carbohydrate-Substituted Indenoisoquinoline Topoisomerase I Inhibitors and Improved Syntheses of the Experimental Anticancer Agents Indotecan (LMP400) and Indimitecan (LMP776)

et al. 2014

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Carbohydrate moieties were strategically transported from the indolocarbazole topoisomerase I (Top1) inhibitor class to the indenoisoquinoline system in search of structurally novel and potent Top1 inhibitors. The syntheses and biological evaluation of 20 new indenoisoquinolines glycosylated with linear and cyclic sugar moieties are reported. Aromatic ring substitution with 2,3-dimethoxy-8,9-methylenedioxy or 3-nitro groups exerted strong effects on antiproliferative and Top1 inhibitory activities. While the length of the carbohydrate side chain clearly correlated with antiproliferative activity, the relationship between stereochemistry and biological activity was less clearly defined. Twelve of the new indenoisoquinolines exhibit Top1 inhibitory activity equal to or better than that of camptothecin. An advanced synthetic intermediate from this study was also used to efficiently prepare indotecan (LMP400) and indimitecan (LMP776), two anticancer agents currently under investigation in a Phase I clinical trial at the National Institutes of Health.

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Topoisomerase I Inhibitors: Chemical Biology

Cited by 2 publications

References 119 publications

Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Alterations in Cell-Extracellular Matrix Interactions during Progression of Cancers

Synthesis and Biological Evaluation of New Carbohydrate-Substituted Indenoisoquinoline Topoisomerase I Inhibitors and Improved Syntheses of the Experimental Anticancer Agents Indotecan (LMP400) and Indimitecan (LMP776)

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