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

Dingbiao Zou, Yatao Qiu, Zhengchao Tu, Chenzhong Liao, Jinfeng Luo, Qingqing Meng, Risheng Yao, Zheng Li, Sheng Jiang

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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 0.65 μM, 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.

Original languageEnglish (US)
Pages (from-to)823-832
Number of pages10
JournalScience China Chemistry
Issue number6
StatePublished - Jun 2014


  • anticancer agents
  • Bcr-Abl
  • chronic myeloid leukemia (CML)
  • imatinib resistance

ASJC Scopus subject areas

  • Chemistry(all)

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