2012
DOI: 10.1158/0008-5472.can-11-2303
|View full text |Cite
|
Sign up to set email alerts
|

Dinitroazetidines Are a Novel Class of Anticancer Agents and Hypoxia-Activated Radiation Sensitizers Developed from Highly Energetic Materials

Abstract: In an effort to develop cancer therapies that maximize cytotoxicity, while minimizing unwanted side effects, we studied a series of novel compounds based on the highly energetic heterocyclic scaffold, dinitroazetidine. In this study, we report the preclinical validation of 1-bromoacetyl-3,3-dinitroazetidine (ABDNAZ), a representative lead compound currently in a phase I clinical trial in patients with cancer. In tumor cell culture, ABDNAZ generated reactive free radicals in a concentration-and time-dependent m… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

0
93
1

Year Published

2012
2012
2021
2021

Publication Types

Select...
6
1

Relationship

2
5

Authors

Journals

citations
Cited by 91 publications
(94 citation statements)
references
References 25 publications
0
93
1
Order By: Relevance
“…RRx-001-treated U87 xenograft (glioma) specimens analyzed immunohistochemically with anti-CD-31, a marker for vasculature, overexpressed in the neovascular tumor bed, and a fluorescent carbocyanine dye, DiOC7, that stains cells immediately adjacent to blood vessels and, thus, outlines perfused tumor vasculature, demonstrated increased vessel perfusion [29]. In a separate study of syngeneic SCCVII tumors, quantitative measurements of the flow of an ultrasound microbubble contrast agent demonstrated a significant enhancement of tumor perfusion following treatment with three different doses (3, 6, 12 mg/kg) of RRx-001 compared to control mice, reaching a peak at 6 h after treatment, and returning to baseline within 72 h [1].…”
Section: Vascular 'Normalization' and Increased Tumor Blood Flowmentioning
confidence: 96%
See 2 more Smart Citations
“…RRx-001-treated U87 xenograft (glioma) specimens analyzed immunohistochemically with anti-CD-31, a marker for vasculature, overexpressed in the neovascular tumor bed, and a fluorescent carbocyanine dye, DiOC7, that stains cells immediately adjacent to blood vessels and, thus, outlines perfused tumor vasculature, demonstrated increased vessel perfusion [29]. In a separate study of syngeneic SCCVII tumors, quantitative measurements of the flow of an ultrasound microbubble contrast agent demonstrated a significant enhancement of tumor perfusion following treatment with three different doses (3, 6, 12 mg/kg) of RRx-001 compared to control mice, reaching a peak at 6 h after treatment, and returning to baseline within 72 h [1].…”
Section: Vascular 'Normalization' and Increased Tumor Blood Flowmentioning
confidence: 96%
“…Multiple lines of evidence indicate that metabolites of RRx-001 cross the blood-brain barrier: (1) in an ADME study with 14 C-labeled RRx-001, radioactivity was detected in the CNS [8]; (2) in an ongoing Phase I/II trial acronymed BRAINSTORM, a significant reduction in the Dynamic contrast-enhancedmagnetic resonance imaging (DCE-MRI)-derived volume transfer constant, K trans , has been demonstrated in multiple patients after one dose of single agent RRx-001, indicative of reduced vascular permeability; and (3) the combination of RRx-001 with artemisinin, in an experimental cerebral malaria model, synergistically decreased animal mortality, neurocognitive sequelae, cerebral vascular changes, and inflammatory cell accumulation in brain microvessels [10].…”
Section: Chemical Structurementioning
confidence: 99%
See 1 more Smart Citation
“…RRx-001, a novel, nonexplosive molecule modified from a class of solid rocket propellants, has shown promise as a novel cancer therapeutic agent in a number of cell lines and tumor models (Bednarski et al, 2009;Ning et al, 2012). In mouse models, RRx-001 administered intravenously as a single agent was equipotent to cisplatin while better tolerated.…”
Section: Introductionmentioning
confidence: 99%
“…In mouse models, RRx-001 administered intravenously as a single agent was equipotent to cisplatin while better tolerated. RRx-001 also showed activity as a radiosensitizer in both in vitro and in vivo models (Ning et al, 2012). The activity of RRx-001 is thought to be associated with a nucleophilic substitution by circulating thiol compounds and covalent binding of RRx-001 to cysteinyl residues in Hb, followed by the generation of nitrogen oxides.…”
Section: Introductionmentioning
confidence: 99%