Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors

Chun Ho Park, Chulho Lee, Jee Sun Yang, Bo Young Joe, Kwangwoo Chun, Hyuntae Kim, Hye Yun Kim, Jong Soon Kang, Jangik I. Lee, Myung Hwa Kim, Gyoonhee Han

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Inactivation of the NF-κB signaling pathway by inhibition of IKKβ is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKβ inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKβ was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1 μM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.

Original languageEnglish
Pages (from-to)2655-2660
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Issue number12
Publication statusPublished - 2014 Jun 15

Bibliographical note

Funding Information:
This research was supported by Grants from the Translational Research Center for Protein Function Control ( 2009-0083522 ), the Ministry of Health & Welfare ( A120478 ), the National Research Foundation funded by Ministry of Education ( NRF-2013R1A1A2008165 ) and the Ministry of Science, ICT & Future Planning ( NRF-2006-511-C00060 and NRF-2013M3A6A4072536 ), Republic of Korea, and the Yonsei University Research Fund of 2012.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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