Biological evaluation of 2-methylpyrimidine derivatives as active pan Bcr-Abl inhibitors

We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibito...

Full description

Saved in:
Bibliographic Details
Published in:Science China. Chemistry 2014-06, Vol.57 (6), p.823-832
Main Authors: Zou, DingBiao, Qiu, YaTao, Tu, ZhengChao, Liao, ChenZhong, Luo, JinFeng, Meng, QingQing, Yao, RiSheng, Li, Zheng, Jiang, Sheng
Format: Article
Language:English
Subjects:
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
IC50
K562细胞
Kinases
合成化合物
嘧啶衍生物
平移
抑制剂
抑制活性
生物学评价
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We designed a series of 2-methylpyrimidine derivatives as new BCR-ABL inhibitors using scaffold-hopping strategy.These synthetic compounds exhibited significant inhibition against a broad spectrum of Bcr-Abl mutants including the gatekeeper T315I mutant.Compound 7u showed very potent kinase inhibitory activities against Bcr-Abl WT,Bcr-Abl E255K,Bcr-Abl Q252H,Bcr-Abl G250E and Bcr-Abl T315I,with IC50 values of 0.13 nM,0.17 nM,0.24 nM,0.19 nM and 0.65μM,respectively.This compound also displayed anti-proliferation activity against K562 cell line with an IC50 value of 1.1 nM,thus representing a new lead for further optimization.
ISSN:1674-7291
1869-1870
DOI:10.1007/s11426-013-5011-9