当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells.

Structure-based modification of carbonyl-diphenylpyrimidines (Car-DPPYs) as a novel focal adhesion kinase (FAK) inhibitor against various stubborn cancer cells.

Abstract：

:A family of carbonyl-substituted diphenylpyrimidine derivatives (Car-DPPYs) with strong activity against focal adhesion kinase (FAK), were described in this manuscript. Among them, compounds 7a (IC50 = 5.17 nM) and 7f (IC50 = 2.58 nM) displayed equal anti-FAK enzymatic activity to the lead compound TAE226 (6.79 nM). In particular, compound 7a also exhibited strong antiproliferative activity against several stubborn cancer cells, including AsPC-1 cells (IC50 = 0.105 μM), BxPC-3 cells (IC50 = 0.090 μM), and MCF-7/ADR cells (IC50 = 0.59 μM). Additionally, compound 7a also showed great antitumor efficacy in vivo via aAsPC-1 cancer Xenograft mouse model. The preliminary mechanism study by Western blot analysis revealed that 7a repressed FAK phosphorylation in AsPC cancer cells. Taken together, the results indicate that compound 7a may serve as a promising preclinical candidate for treatment of stubborn cancers.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Wang L,Ai M,Yu J,Jin L,Wang C,Liu Z,Shu X,Tang Z,Liu K,Luo H,Guan W,Sun X,Ma X

doi

10.1016/j.ejmech.2019.04.004

subject

Has Abstract

pub_date

2019-06-15 00:00:00

pages

154-162

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(19)30303-4

journal_volume

172

pub_type

杂志文章

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