Molecular Diversity

, Volume 18, Issue 2, pp 403–409 | Cite as

Structural modification of an EGFR inhibitor that showed weak off-target activity against RET leading to the discovery of a potent RET inhibitor

  • Qi-Zheng Sun
  • Yong Xu
  • Jing-Jing Liu
  • Chun-Hui Zhang
  • Ze-Rong Wang
  • Ren-Lin Zheng
  • Wen-Jing Wang
  • Lin-Li Li
  • Sheng-Yong Yang
Short Communication


Here, we describe the structural optimization of a known EGFR inhibitor (compound 1) that showed weak off-target activity against RET. Twenty-six analogs of 1 were synthesized. SAR analysis led to the discovery of several compounds that showed considerable potency against the RET-dependent thyroid cancer cell line TT. Kinase inhibitory potency was then measured for the most active compound (2u) in the cellular assay. The results showed that 2u is a potent RET inhibitor with an \(\hbox {IC}_{50}\) value of 7 nM.


Thyroid cancer Rearranged during transfection (RET) Anticancer agents EGFR Kinases Kinase inhibitorss 



This work was supported by the 863 Hi- Tech Program (Nos. 2012AA020301, 2012AA020308), the National Natural Science Foundation of China (81172987), and SRFDP (20100181110025)

Supplementary material

11030_2014_9508_MOESM1_ESM.pdf (1.3 mb)
Supplementary material 1 (pdf 1374 KB)


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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Qi-Zheng Sun
    • 1
  • Yong Xu
    • 1
  • Jing-Jing Liu
    • 1
  • Chun-Hui Zhang
    • 1
  • Ze-Rong Wang
    • 2
  • Ren-Lin Zheng
    • 3
  • Wen-Jing Wang
    • 1
  • Lin-Li Li
    • 2
  • Sheng-Yong Yang
    • 1
  1. 1.State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical SchoolSichuan UniversityChengduChina
  2. 2.West China School of pharmacySichuan UniversityChengduChina
  3. 3.School of Life Science and EngineeringSouthwest University of Science and TechnologyMianyangChina

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