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Design and synthesis of Lapatinib derivatives containing a branched side chain as HER1/HER2 targeting antitumor drug candidates.

Abstract：

:A series of Lapatinib derivatives were designed and prepared by changing the straight alkyl side chain of Lapatinib into a branched one. ELISA assay and western blot analysis showed that these derivatives can significantly inhibit HER1/HER2 as well as their downstream signal transduction proteins. In vitro cytotoxicity assay revealed that these compounds had potent cytotoxic effect against the HER1/HER2-overexpressing cancer cells. A representive compound, 2i, showed potent in vivo antitumor activity comparable to Lapatinib, which was found to block the cell-cycle progression of BT474 cells in the G1 phase causing tumor cell apoptosis in the flow cytometry study. Moreover, the pharmacokinetic investigation on 2i also indicated it had a good performance on both absorption and elimination profiles.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Lyu A,Fang L,Gou S

doi

10.1016/j.ejmech.2014.10.006

subject

Has Abstract

pub_date

2014-11-24 00:00:00

pages

631-42

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00932-5

journal_volume

87

pub_type

杂志文章

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