Discovery of thienopyrimidine-based FLT3 inhibitors from the structural modification of known IKKß inhibitors.
Bioorg Med Chem Lett
; 24(12): 2655-60, 2014 Jun 15.
Article
em En
| MEDLINE
| ID: mdl-24813730
ABSTRACT
Inactivation of the NF-κB signaling pathway by inhibition of IKKß 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 IKKß 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 IKKß 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
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Quinase I-kappa B
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Tirosina Quinase 3 Semelhante a fms
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Bibliotecas de Moléculas Pequenas
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article