当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.

A small molecule inhibitor, 1,2,4,5-benzenetetraamine tetrahydrochloride, targeting the y397 site of focal adhesion kinase decreases tumor growth.

Abstract：

:Focal adhesion kinase (FAK) is a nonreceptor kinase that is overexpressed in many types of tumors. We developed a novel cancer-therapy approach, targeting the main autophosphorylation site of FAK, Y397, by computer modeling and screening of the National Cancer Institute (NCI) small molecule compounds database. More than 140,000 small molecule compounds were docked into the N-terminal domain of the FAK crystal structure in 100 different orientations that identified 35 compounds. One compound, 14 (1,2,4,5-benzenetetraamine tetrahydrochloride), significantly decreased viability in most of the cells to the levels equal to or higher than control FAK inhibitor 1a (2-[5-chloro-2-[2-methoxy-4-(4-morpholinyl)phenylamino]pyrimidin-4-ylamino]-N-methylbenzamide, TAE226) from Novartis, Inc. Compound 14 specifically and directly blocked phosphorylation of Y397-FAK in a dose- and time-dependent manner. It increased cell detachment and inhibited cell adhesion in a dose-dependent manner. Furthermore, 14 effectively caused breast tumor regression in vivo. Thus, targeting the Y397 site of FAK with 14 inhibitor can be effectively used in cancer therapy.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Golubovskaya VM,Nyberg C,Zheng M,Kweh F,Magis A,Ostrov D,Cance WG

doi

10.1021/jm800483v

subject

Has Abstract

pub_date

2008-12-11 00:00:00

pages

7405-16

issue

23

eissn

0022-2623

issn

1520-4804

journal_volume

51

pub_type

杂志文章

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