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

Cited 22 time in scopus
Metadata Downloads
Title
Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKbeta inhibitors
Author(s)
C H Park; C Lee; J S Yang; B Y Joe; K Chun; H Kim; H Y Kim; Jong Soon Kang; J I Lee; M H Kim; G Han
Bibliographic Citation
Bioorganic & Medicinal Chemistry Letters, vol. 24, no. 12, pp. 2655-2660
Publication Year
2014
Abstract
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.
Keyword
Acute myeloid leukemia (AML)Anti-inflammationFLT3IKKβThienopyrimidine
ISSN
0960-894X
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.bmcl.2014.04.058
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.