N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors

Raeppel, Stéphane; Claridge, Stephen; Saavedra, Oscar M.; Gaudette, Frédéric; Zhan, Lijie; Mannion, Michael R.; Zhou, Nancy; Raeppel, Franck; Granger, Marie-Claude; Isakovic, Ljubomir; Déziel, Robert; Nguyen, Hannah; Beaulieu, Normand; Beaulieu, Carole; Dupont, Isabelle; Robert, Mathieu; Lefèbvre, Sylvain; Dubay, Marja; Rahil, Jubrail; Wang, Jinru; Ste-Croix, Hélène; MacLeod, A. Robert; Besterman, Jeffrey M.; Vaisburg, A. F.

doi:10.1016/j.bmcl.2009.01.068

Cited by 33 publications

(13 citation statements)

References 41 publications

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“…[12][13][14][15] Magnetoliposomes are specially promising as nanocarriers for potential antitumor drugs. Thienopyridine derivatives have been reported as possessing antiangiogenic, [16][17][18][19][20][21] antitumor, [21][22][23][24][25][26][27][28][29] or both activities. 30 Among the potential antitumor di(hetero)arylamines in the thieno [3,2-b]pyridine series, prepared earlier by some of us, the ones with an o-methoxy or m-methoxy groups relative to the NH (compounds 1 and 2, Fig.…”

Section: Introductionmentioning

confidence: 99%

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

et al. 2017

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Magnetoliposomes containing superparamagnetic manganese ferrite nanoparticles were tested as nanocarriers for two new promising antitumor drugs, a N-(3-methoxyphenyl)thieno[3,2-b]pyridin-7-amine (1) and a N-(2-methoxy-phenyl)thieno[3,2-b]pyridin-7-amine (2). The fluorescence emission of both compounds was studied in different polar and non-polar media, evidencing a strong intramolecular charge transfer character of the excited state of both compounds. These in vitro potent antitumor thienopyridine derivatives were successfully incorporated in both aqueous and solid magnetoliposomes, with encapsulation efficiencies higher than 75%. The magnetic properties of magnetoliposomes containing manganese ferrite nanoparticles were measured for the first time, proving a superparamagnetic behaviour. Growth inhibition assays on several human tumor cell lines showed very low GI 50 values for drug-loaded aqueous magnetoliposomes, comparing in most cell lines with the ones previously obtained using the neat compounds. These results are important for future drug delivery applications using magnetoliposomes in oncology, through a dual therapeutic approach (simultaneous chemotherapy and magnetic hyperthermia).

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Section: Introductionmentioning

confidence: 99%

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

et al. 2017

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“…Small-molecule c-Met kinase inhibitors and antibodies targeting c-Met or HGF have exhibited antitumor activities in preclinical models (15)(16)(17)(18)(19)(20)(21)(22)(23). Some of these agents are undergoing clinical development (22,23).…”

Section: Introductionmentioning

confidence: 99%

MK-2461, a Novel Multitargeted Kinase Inhibitor, Preferentially Inhibits the Activated c-Met Receptor

et al. 2010

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“…The MTD is 3.6 mg/kg and common side effects include hypertension and fatigue. The agent is being evaluated in papillary renal cell carcinoma, gastric and head and neck cancers [71,72].…”

Section: Targeting Met Catalytic Site: the Role Of Small Moleculesmentioning

confidence: 99%

Targeting the MET oncogene in cancer and metastases

Stella

Benvenuti

Comoglio

2010

Expert Opinion on Investigational Drugs

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Importance of the field: 'Invasive growth' is a genetic program involved in embryonic development and adult organ regeneration and usurped by cancer cells. Although its control is complex, tumor-and context-specific and regulated by several cytokines and growth factors, the role played by the MET oncogene is well documented. In human cancers the contribution of MET to invasive growth is mainly through overexpression, driven by unfavorable microenvironmental conditions. MET activation confers a selective advantage to neoplastic cells in tumor progression and drug resistance. A subset of tumors feature alterations of the MET gene and a consequent MET-addicted phenotype. Areas covered in this review: The molecular basis and rationale of MET inhibition in cancer and metastases are discussed. A number of molecules designed to block MET signaling are under development and several Phase II trials are ongoing. What the reader will gain: Knowledge of the state of the art of anti-MET targeted approaches and the molecular basis and strategies to select patients eligible for treatment with MET inhibitors. Take home message: Due to its versatile functions MET is a promising candidate for cancer therapy. Understanding molecular mechanisms of sensitization and resistance to MET inhibitors is a priority to guide tailored therapies and select patients that are most likely to achieve a clinical benefit.

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N-(3-fluoro-4-(2-arylthieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-3-phenylimidazolidine-1-carboxamides: A novel series of dual c-Met/VEGFR2 receptor tyrosine kinase inhibitors

Cited by 33 publications

References 41 publications

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

Magnetoliposomes as carriers for promising antitumor thieno[3,2-b]pyridin-7-arylamines: photophysical and biological studies

MK-2461, a Novel Multitargeted Kinase Inhibitor, Preferentially Inhibits the Activated c-Met Receptor

Targeting the MET oncogene in cancer and metastases

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