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Cited by 364

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5- (tetrahydro-2 H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src/Abl Kinase Inhibitor

Open access
Hennequin, Laurent F., Allen, Jack, Breed, Jason, Curwen, Jon, Fennell, Michael, Green, Tim P., Lambert-van der Brempt, Christine, Morgentin, Rémy, Norman, Richard A., Olivier, Annie, Otterbein, Ludovic, Plé, Patrick A., Warin, Nicolas, Costello, Gerard·2006·Journal of Medicinal Chemistry

Abstract

Src family kinases (SFKs) are nonreceptor tyrosine kinases that are reported to be critical for cancer progression. We report here a novel subseries of C-5-substituted anilinoquinazolines that display high affinity and specificity for the tyrosine kinase domain of the c-Src and Abl enzymes. These compounds exhibit high selectivity for SFKs over a panel of recombinant protein kinases, excellent pharmacokinetics, and in vivo activity following oral dosing. N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine (AZD0530) inhibits c-Src and Abl enzymes at low nanomolar concentrations and is highly selective over a range of kinases. AZD0530 displays excellent pharmacokinetic parameters in animal preclinically and in man (t(1/2) = 40 h). AZD0530 is a potent inhibitor of tumor growth in a c-Src-transfected 3T3-fibroblast xenograft model in vivo and led to a significant increase in survival in a highly aggressive, orthotopic model of human pancreatic cancer when dosed orally once daily. AZD0530 is currently undergoing clinical evaluation in man.

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Registry

Crossref · 10.1021/jm060434q

Cites

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Metadata

Authors
Hennequin, L. F., Allen, J., Breed, J., Curwen, J., Fennell, M., Green, T. P., Lambert-van der Brempt, C., Morgentin, R., Norman, R. A., Olivier, A., Otterbein, L., Plé, P. A., Warin, N., & Costello, G.
Venue
Journal of Medicinal Chemistry
Published
2006-10-04
Volume
49
Issue
22
Pages
6465-6488
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W2024262880
Cited by
364
References
46
FWCI
13.36
Type
journal article
Language
en
Open access
green

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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