Tumorspezifische, Hypoxie‐basierte Aktivierung von EGFR‐Inhibitoren

Karnthaler‐Benbakka, Claudia; Groza, Diana; Kryeziu, Kushtrim; Pichler, Verena; Roller, Alexander; Berger, Walter; Heffeter, Petra; Kowol, Christian R.

doi:10.1002/ange.201403936

Cited by 8 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The advantage of these multiple anticancer activities is that the risks of systemic toxicity caused by administration of more than one anticancer drug would be strongly decreased . Although for most of the cited examples the mechanism by which these drugs inhibit angiogenesis remains elusive, proteins such as growth factors, tubulin, or enzyme cathepsin B seem always to be involved. Even though proteins are considered as non‐traditional targets for metal complexes, some reviews highlight the importance of the metallodrug–protein interaction .…”

Section: Introductionmentioning

confidence: 99%

Exploring the Influence of the Aromaticity on the Anticancer and Antivascular Activities of Organoplatinum(II) Complexes

Zamora

Pérez

Rothemund

et al. 2017

Chemistry A European J

View full text Add to dashboard Cite

A series of new organometallic Pt complexes of the type [Pt(C^N)Cl(DMSO)] (C^N=N,N-dimethyl-1-(2-aryl)methanamine-κ C2,N; aryl=phenyl 2 a, biphenyl 2 b, p-terphenyl 2 c, naphthyl 2 d, anthracenyl 2 e, or pyrenyl 2 f) have been synthesized to explore the influence of the aromaticity on their anticancer activity. The best performers, 2 b and d, are more active than cisplatin (CDDP) in epithelial ovarian carcinoma cells A2780, with 2 d having a higher selectivity factor than CDDP in all the tested cell lines. In addition, all the new compounds overcome the acquired resistance in A2780cisR cells and interestingly, show low micromolar IC values towards the triple negative breast cancer cell line MDA-MB-231 and the highly metastatic 518A2 melanoma cells. This study shows that the hydrophobicity, accumulation into cells, and metal levels on nuclear DNA for the complexes are consistent with their cytotoxicity. Complexes 2 b and d induce apoptosis in a caspase-independent manner and suppress the intracellular ROS generation without modifying the mitochondria membrane potential. In addition, 2 a-f effectively inhibit angiogenesis in the endothelial cell line EA.hy926 at sub-cytotoxic concentrations and 2 b and d show in vivo antivascular effects on the chorioallantoic membrane (CAM) of fertilized SPF-eggs (SPF=specific-pathogen-free). Inhibition of tubulin polymerization and degeneration of cytoskeleton organization in 518A2 melanoma cells are presented as a preliminary mechanism of its antimetastatic activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Exploring the Influence of the Aromaticity on the Anticancer and Antivascular Activities of Organoplatinum(II) Complexes

Zamora

Pérez

Rothemund

et al. 2017

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…By exploiting the differences in the chemical environment that exist between the drug's target site and systemic circulation, off‐target reactions can be minimized. Kowol and co‐workers designed cobalt‐modified erlotinib derivatives as caged EGFR inhibitors by taking advantage of Co III → Co II reduction chemistry in the hypoxic environment observed in many solid tumors . The chemically inert octahedral Co III center in compound 9 (Figure ) is redox‐stable in normoxic tissue, and its bulkiness prevents the inhibitor from entering the kinase's ATP‐binding pocket.…”

Section: Metal Complexes As Protein Kinase Inhibitorsmentioning

confidence: 99%

Metal‐Containing Pharmacophores in Molecularly Targeted Anticancer Therapies and Diagnostics

Yang

Bierbach

2016

Eur J Inorg Chem

View full text Add to dashboard Cite

Molecularly targeted therapeutic agents make up an important class of oncology drugs that are used either alone, or in combination with classical cytotoxic agents, to combat many solid tumors and hematological cancers. Their targets in cancer cells are proteins that are encoded by oncogenes, which regulate cell growth, survival, and proliferation. These include a number of signal-transducing and angiogenesis-related kinases, hormone receptors, and certain cell-surface antigens. Targeting of cancer cells harboring oncogenic molecular targets with precision medicines, while sparing the vast majority of normal healthy cells, has led to promising new treatments for cancer

show abstract

Tumor Inhibition Achieved by Targeting and Regulating Multiple Key Elements in EGFR Signaling Pathway Using a Self‐Assembled Nanoprodrug

Xie

Chen

et al. 2018

Adv Funct Materials

View full text Add to dashboard Cite

Comprehensive understanding of signaling pathways regulating cancer progression has led to tremendous advances of molecularly targeted therapies. The epidermal growth factor receptor (EGFR) pathway is an attractive target for cancer therapy, and targeting multiple key elements in the pathway may further facilitate therapeutic efficacy. Here, an EGFR‐targeted nanoprodrug is demonstrated for in vivo imaging and tumor inhibition, which is assembled by a disulfide‐bridged quercetin (QSSQ) and an EGFR inhibitor erlotinib. QSSQ is synthesized via chemical manipulation of multiple phenolic hydroxyl groups on quercetin; and the nanoprodrug is then fabricated through the disulfide‐facilitated assembly of QSSQ and erlotinib. The nanoprodrug is of high drug loading (87.3%) since its only inert component is the disulfide linker. The nanoprodrug is stable in physiological environment, whereas overexpressed glutathione in tumor tissue breaks the disulfide bridge, thereby disrupting the nanostructure and releasing active drugs quercetin and erlotinib. Upon release, erlotinib serves as an active drug blocking the EGFR tyrosine kinase, and quercetin generates strong aggregation‐induced emission of fluorescence for imaging drug release and acts as another drug inhibiting the downstream EFGR signaling, as evidenced by Western blotting analyses. The combined action thereof results in remarkable antitumor efficacy toward xenograft tumor‐bearing mice.

show abstract

Tumorspezifische, Hypoxie‐basierte Aktivierung von EGFR‐Inhibitoren

Cited by 8 publications

References 25 publications

Exploring the Influence of the Aromaticity on the Anticancer and Antivascular Activities of Organoplatinum(II) Complexes

Exploring the Influence of the Aromaticity on the Anticancer and Antivascular Activities of Organoplatinum(II) Complexes

Metal‐Containing Pharmacophores in Molecularly Targeted Anticancer Therapies and Diagnostics

Tumor Inhibition Achieved by Targeting and Regulating Multiple Key Elements in EGFR Signaling Pathway Using a Self‐Assembled Nanoprodrug

Contact Info

Product

Resources

About