Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors.
Basic Information
ID: ALA3286226
Journal: Bioorg Med Chem Lett
Title: Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKβ inhibitors.
Authors: Park CH, Lee C, Yang JS, Joe BY, Chun K, Kim H, Kim HY, Kang JS, Lee JI, Kim MH, Han G.
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 1μM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.
CiteXplore: 24813730
DOI: 10.1016/j.bmcl.2014.04.058
Patent ID: ┄