Rhenium and Technetium-oxo Complexes with Thioamide Derivatives of Pyridylhydrazine Bifunctional Chelators Conjugated to the Tumour Targeting Peptides Octreotate and Cyclic-RGDfK

North, Andrea J.; Karas, John A.; Michelle, T.; Blower, Philip J.; Ackermann, Uwe; White, Jonathan M.; Donnelly, Paul S.

doi:10.1021/acs.inorgchem.7b01247

Cited by 23 publications

(29 citation statements)

References 71 publications

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“…To better understand the potential e cacy of the selected Rhenium compound in a tumour setting, we tested the effect of JVG045 on primary cell cultures derived from pancreatic ductal adenocarcinoma isolated from KrasLSL.G12D/+; p53R172H/+; PdxCretg/+ (or KPC) mice. We found that JVG045 impairs KPC primary cell growth in a dose-dependent manner (Fig 3A,B), reaching statistical signi cance at 5 and 10μM (One-way ANOVA F (4,20) =11.87, p<0.0001). We also tested the effect of 10mM JVG045 on anchorage independent soft agar colony formation, which measures the ability of cancer cells to grow and to proliferate without support on a solid surface (29,43).…”

Section: Resultsmentioning

confidence: 81%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

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Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes. Here we describe the potential anticancer activity of rhenium-based complexes with preclinical efficacy in different types of solid malignancies.Methods: Kinase profile assay of rhenium complexes. Toxicology studies using zebrafish. Analysis of the growth of pancreatic cancer cell line-derived xenografts generated in zebrafish and in mice upon exposure to rhenium compounds.Results: We describe rhenium complexes which block cancer proliferation in vitro by inhibiting the signalling cascade induced by FGFR and Src. Initially, we tested the toxicity of rhenium complexes in vivo using a zebrafish model and identified one compound that displays anticancer activity with low toxicity even in the high micromolar range. Notably, the rhenium complex has anticancer activity in very aggressive cancers such as pancreatic ductal adenocarcinoma and neuroblastoma. We demonstrate the potential efficacy of this complex via a significant reduction in cancer growth in mouse xenografts.Conclusions: Our findings provide a basis for the development of rhenium-based chemotherapy agents with enhanced selectivity and limited side effects compared to standard platinum-based drugs.

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Section: Resultsmentioning

confidence: 81%

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Domenichini

Casari

Simpson

et al. 2020

Preprint

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“…Enlarging this finding to the corresponding nicotinylthiosemicarbazide ligand offered an additional free carboxylic group available to append targeting molecule. Such a strategy has been used to tether the Re(V) to Tyr3-octreotate and cyclic-RGD tumor targeting peptides [32]. Many heterobimetallic compounds have been synthesized…”

Section: Chemical Structuresmentioning

confidence: 99%

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

Collery¹,

Desmaële

Veena

2019

CPD

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Background: Many rhenium (Re) complexes with potential anticancer properties have been synthesized in the recent years with the aim to overcome the clinical limitations of platinum agents. Re(I) tricarbonyl complexes are the most common but Re compounds with higher oxidation states have also been investigated, as well as hetero-metallic complexes and Re-loaded self-assembling devices. Many of these compounds display promising cytotoxic and phototoxic properties against malignant cells but all Re compounds are still at the stage of preclinical studies. Methods: The present review focused on the rhenium based cancer drugs that were in preclinical and clinical trials were examined critically. The detailed targeted interactions and experimental evidences of Re compounds reported by the patentable and non-patentable research findings used to write this review. Results: In the present review, we described the most recent and promising rhenium compounds focusing on their potential mechanism of action including, phototoxicity, DNA binding, mitochondrial effects, oxidative stress regulation or enzyme inhibition. Many ligands have been described that modulating the lipophilicity, the luminescent properties, the cellular uptake, the biodistribution, and the cytotoxicity, the pharmacological and toxicological profile. Conclusion: Re-based anticancer drugs can also be used in targeted therapies by coupling to a variety of biologically relevant targeting molecules. On the other hand, combination with conventional cytotoxic molecules, such as doxorubicin, allowed to take into profit the targeting properties of Re for example toward mitochondria. Through the example of the diseleno-Re complex, we showed that the main target could be the oxidative status, with a down-stream regulation of signaling pathways, and further on selective cell death of cancer cells versus normal cells.

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“…Re in this form (Figure 6) [69]. proven itself as a versatile radiolabelling synthon for coupling to a range of chelators conjugated to targeting molecules, and for direct labelling of proteins (Figure 7).…”

Section: Stable Well-defined Chelated Derivative With the Square Pyrmentioning

confidence: 99%

Rhenium-188 Radiochemistry: Challenges and Prospects

Blower¹

2017

Int. J. Nucl. Medi. Res.

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After a lull in development of new chemistry for rhenium-188 and technetium-99m since 2000, there has been new investment in production facilities for Mo-99/Tc-99m coupled with increasing interest in rhenium-188 radionuclide therapy, particularly in developing countries. Much of the chemistry developed in the 1990s is not readily amenable to supporting modern radiopharmaceutical development, which places increased emphasis on molecular targeted radiopharmaceuticals. Consequently there is a need for new radiolabelling chemistry to incorporate these radionuclides into biomolecules using simple, kit-based methodology. This review provides an update on progress towards simple rhenium-188 labelling methods since 2000.

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Rhenium and Technetium-oxo Complexes with Thioamide Derivatives of Pyridylhydrazine Bifunctional Chelators Conjugated to the Tumour Targeting Peptides Octreotate and Cyclic-RGDfK

Cited by 23 publications

References 71 publications

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Rhenium N-heterocyclic Carbene Complexes Block Growth of Aggressive Cancers by Inhibiting FGFR- and SRC-Mediated Signalling

Design of Rhenium Compounds in Targeted Anticancer Therapeutics

Rhenium-188 Radiochemistry: Challenges and Prospects

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