Phase I clinical study of 9-hydroxy-2N-methyl-ellipticinium acetate (NSC-264137) administered on a 5-day i.v. schedule

Dodion, Pierre; Rozencweig, Marcel; Nicaise, Claude; Piccart, Martine; Cumps, Evelyne; Crespeigne, N.; Kisner, Daniel L.; Kenis, Yvon

doi:10.1016/0277-5379(82)90220-6

Cited by 24 publications

(13 citation statements)

References 2 publications

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“…Although ellipticine is also an antitumor agent, it was rarely administrated to patients because of its mutagenesis activity and poor solubility. However, its chemical derivatives have more applications in clinics (8,10).…”

Section: Discussionmentioning

confidence: 99%

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

González-Molleda

Yan

Yuan

2012

Antimicrob Agents Chemother

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. To assess the importance of these topoisomerases in viral lytic replication, shRNA-mediated gene silencing was used. Depletion of Topo I and II severely inhibited viral lytic DNA replication as well as virion production, suggesting essential roles of these cellular proteins in viral DNA replication. The discovery of Topo I and II as enzymes indispensable for KSHV DNA replication raises a possibility that these cellular proteins could be new targets of therapeutic approaches to halt KSHV replication and treat KSHV-associated diseases. In this report, we examined one Topo I inhibitor and several Topo II inhibitors (inclusive of Topo II poison and catalytic inhibitors) as potential therapeutic agents for blocking KSHV replication. The Topo II catalytic inhibitors in general exhibited marked inhibition on KSHV replication and minimal cytotoxicity. In particular, novobiocin, with the best selectivity index (SI ‫؍‬ 31.62) among the inhibitors tested in this study, is effective in inhibiting KSHV DNA replication and virion production but shows little adverse effect on cell proliferation and cycle progression in its therapeutic concentration, suggesting its potential to become an effective and safe drug for the treatment of human diseases associated with KSHV infection.

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Section: Discussionmentioning

confidence: 99%

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

González-Molleda

Yan

Yuan

2012

Antimicrob Agents Chemother

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“…[ 22 ] Third, the challenges encountered during early clinical trials of its derivatives suggest a strong need of an effective delivery system. [30][31][32] The complexation of ellipticine with APP8 at different peptide concentrations (4.4-436 μ M ) was fi rst studied by examining the ellipticine emission fl uorescence spectra ( Figure 4 ). Ellipticine is water insoluble, so ellipticine in water (EPT-H) barely had fl uorescence signals.…”

Section: Drug Delivery Potential Of App8mentioning

confidence: 99%

Amino Acid Pairing for De Novo Design of Self‐Assembling Peptides and Their Drug Delivery Potential

Fung

Yang

Sadatmousavi

et al. 2011

Adv Funct Materials

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Molecular self-assembly has emerged as the "bottom-up" engineering route to fabricate functional supramolecules for diverse applications. The design of molecular building units becomes critical in determining the structure, properties, and function of the resulting assemblies. Here, a de novo design principle of amino acid pairing (AAP) to generate new classes of self-assembling peptides (SAPs) is presented. In this study, the AAP focuses on hydrogen bonding, and ionic and hydrophobic interactions among amino acid pairs. With solely hydrogen bond pairs, SAPs can be constructed with only two amino acids. With all three AAP strategies (hydrogen bonds, ionic and hydrophobic pairs), a short novel SAP is constructed. This peptide can self-assemble into β -sheet-rich nanofi bers with a relatively low "critical aggregation concentration (CAC)" of ∼ 10 μ M . It also shows the ability to stabilize and deliver the hydrophobic anticancer agent ellipticine in aqueous solution. The peptide-drug complexes/co-assemblies exhibit anticancer activity against human lung carcinoma cells A549 and breast cancer cells MCF-7, and have good dilution stability. The presented AAP design provides a new strategy to fabricate functional supramolecules with potential applications in nanomedicine.

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“…It was concluded that administration of a daily dose of 15-80 mg/m 2 daily for 5 days once every 3 weeks did not offer any appreciable advantage over the usual weekly regimen in terms of toxicity and response [145]. However, Rouesse et al concluded that a regimen of 80 mg/m 2 daily for 3 days once every 3 weeks was as active as, and less toxic than the traditional weekly schedule in treating advanced breast cancer [144].…”

Section: Clinical Trialsmentioning

confidence: 96%

“…Other phase I and phase II trials compared different dosing regimens for elliptinium acetate [144,145]. It was concluded that administration of a daily dose of 15-80 mg/m 2 daily for 5 days once every 3 weeks did not offer any appreciable advantage over the usual weekly regimen in terms of toxicity and response [145].…”

Section: Clinical Trialsmentioning

confidence: 99%

Emerging Targets in the Bioactivity of Ellipticines and Derivatives

O'Sullivan

Miller

Deane

et al. 2013

Studies in Natural Products Chemistry

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Phase I clinical study of 9-hydroxy-2N-methyl-ellipticinium acetate (NSC-264137) administered on a 5-day i.v. schedule

Cited by 24 publications

References 2 publications

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

Potent Antiviral Activity of Topoisomerase I and II Inhibitors against Kaposi's Sarcoma-Associated Herpesvirus

Amino Acid Pairing for De Novo Design of Self‐Assembling Peptides and Their Drug Delivery Potential

Emerging Targets in the Bioactivity of Ellipticines and Derivatives

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