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Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase inhibitors by c-Src-based high-throughput screening
Lin L.-G.; Xie H.; Li H.-L.; Tong L.-J.; Tang C.-P.; Ke C.-Q.; Liu Q.-F.; Lin L.-P.; Geng M.-Y.; Jiang H.; Zhao W.-M.; Ding J.; Ye Y.
2008-08-14
Source PublicationJournal of Medicinal Chemistry
ISSN00222623
Volume51Issue:15Pages:4419-4429
Abstract

Protein tyrosine kinase (PTK) inhibitors represent emerging therapeutics for cancer chemoprevention. In our study, hematoxylin (26) was identified as one of the most remarkable c-Src inhibitors in an orthogonal compound-mixing library (32200 compounds) by using an ELISA-based automated high-throughput screening (HTS) strategy. Interestingly, hematoxylin was found to be an ATP competitive broad-spectrum PTK inhibitor in vitro, with IC values ranging from nanomolar to micromolar level. Further studies showed that such inhibition was associated with the PTK phosphorylation and subsequent downstream signaling pathways. The structure-activity relationship assessment of the PTK inhibitory potency of hematoxylin analogues isolated from Heamatoxylon campechianum was in good agreement with the result of concurrent molecular docking simulation: the catechol moiety in ring A and the hematoxylin-like three-dimensional structure were essential for c-Src-targeted activities. Hematoxylin and its natural analogues were substantially validated to function as a new class of PTK inhibitors. © 2008 American Chemical Society.

DOI10.1021/jm701501x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal
WOS IDWOS:000258289800011
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Cited Times [WOS]:52   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
AffiliationShanghai Institute for Biological Sciences Chinese Academy of Sciences
Recommended Citation
GB/T 7714
Lin L.-G.,Xie H.,Li H.-L.,et al. Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase inhibitors by c-Src-based high-throughput screening[J]. Journal of Medicinal Chemistry,2008,51(15):4419-4429.
APA Lin L.-G..,Xie H..,Li H.-L..,Tong L.-J..,Tang C.-P..,...&Ye Y..(2008).Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase inhibitors by c-Src-based high-throughput screening.Journal of Medicinal Chemistry,51(15),4419-4429.
MLA Lin L.-G.,et al."Naturally occurring homoisoflavonoids function as potent protein tyrosine kinase inhibitors by c-Src-based high-throughput screening".Journal of Medicinal Chemistry 51.15(2008):4419-4429.
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