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Chemical Compound Review:

CHEMBL281872 N-(4-bromo-2-fluoro-phenyl)- 6-methoxy-7-[2...

Synonyms: SureCN173259, ZD4190, AC1NS5WP

Wedge, S.R. et al., Nguyen, Q.D. et al., Pradel, C. et al., Brochot, C. et al., Shepherd, F.A., et al.

Shepherd, Brochot, Bessoud, Balvay, Cuénod, Siauve, Bois,

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Disease relevance of ZD4190

Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts [1].

High impact information on ZD4190

ZD4190 is one of a series of VEGF RTK inhibitors that may have utility in the treatment of a range of histologically diverse solid tumor types [2].
ZD4190, a substituted 4-anilinoquinazoline, is a potent inhibitor of KDR and Flt-1 RTK activity, and VEGF stimulated HUVEC proliferation in vitro [2].
As an application, changes in tumor microcirculation parameters were evaluated in mice receiving either an antiangiogenic treatment (ZD4190) or a placebo [3].
ZD4190 is an inhibitor of KDR/Flk-1 that may be evaluated in SCLC [4].
Interestingly, oral administration of the single drug ZD4190 to athymic mice (50 mg/kg/d, once daily) inhibited by 70% the growth of HCT8/S11 tumor cell xenografts [1].

Biological context of ZD4190

Inhibition of VEGF signal transduction. Identification of ZD4190 [5].

Anatomical context of ZD4190

Chronic once-daily oral dosing of ZD4190 to young rats produced a dose-dependent increase in the femoral epiphyseal growth plate area, which may be attributed to the inhibition of VEGF signaling in vivo because vascular invasion of cartilage is a prerequisite to the process of ossification [2].

Associations of ZD4190 with other chemical compounds

We describe the use of perfusion-permeability magnetic resonance imaging (ppMRI) to study hemodynamic parameters in human prostate tumor xenografts, following treatment with the vascular endothelial growth factor-A (VEGF) receptor tyrosine kinase inhibitor, ZD4190 [6].
Combinations between the src tyrosine kinase inhibitor M475271 and ZD4190 or cisplatin resulted in additive therapeutic activity against LNM35 human lung tumor xenografts [1].

Analytical, diagnostic and therapeutic context of ZD4190

Prolonged tumor cytostasis was further demonstrated in a PC-3 xenograft model with 10 weeks of ZD4190 dosing, and upon withdrawal of therapy, tumor growth resumed after a short delay [2].

References

Inhibition of vascular endothelial growth factor (VEGF)-165 and semaphorin 3A-mediated cellular invasion and tumor growth by the VEGF signaling inhibitor ZD4190 in human colon cancer cells and xenografts. Nguyen, Q.D., Rodrigues, S., Rodrigue, C.M., Rivat, C., Grijelmo, C., Bruyneel, E., Emami, S., Attoub, S., Gespach, C. Mol. Cancer Ther. (2006) [Pubmed]
ZD4190: an orally active inhibitor of vascular endothelial growth factor signaling with broad-spectrum antitumor efficacy. Wedge, S.R., Ogilvie, D.J., Dukes, M., Kendrew, J., Curwen, J.O., Hennequin, L.F., Thomas, A.P., Stokes, E.S., Curry, B., Richmond, G.H., Wadsworth, P.F. Cancer Res. (2000) [Pubmed]
Evaluation of antiangiogenic treatment effects on tumors' microcirculation by Bayesian physiological pharmacokinetic modeling and magnetic resonance imaging. Brochot, C., Bessoud, B., Balvay, D., Cuénod, C.A., Siauve, N., Bois, F.Y. Magnetic resonance imaging. (2006) [Pubmed]
Angiogenesis inhibitors in the treatment of lung cancer. Shepherd, F.A. Lung Cancer (2001) [Pubmed]
Inhibition of VEGF signal transduction. Identification of ZD4190. Wedge, S.R., Ogilvie, D.J. Adv. Exp. Med. Biol. (2000) [Pubmed]
Reduced capillary perfusion and permeability in human tumour xenografts treated with the VEGF signalling inhibitor ZD4190: an in vivo assessment using dynamic MR imaging and macromolecular contrast media. Pradel, C., Siauve, N., Bruneteau, G., Clement, O., de Bazelaire, C., Frouin, F., Wedge, S.R., Tessier, J.L., Robert, P.H., Frija, G., Cuenod, C.A. Magnetic resonance imaging. (2003) [Pubmed]

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