Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents

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Title
Synthesis and biological evaluation of novel thieno[2,3-d]pyrimidine-based FLT3 inhibitors as anti-leukemic agents
Author(s)
J S Yang; C H Park; C Lee; H Kim; C Oh; Y Choi; Jong Soon Kang; Ji Eun Yun; J H Jeong; M H Kim; G Han
Bibliographic Citation
European Journal of Medicinal Chemistry, vol. 85, no. C, pp. 399-407
Publication Year
2014
Abstract
The most common mutations in acute myeloid leukemia (AML) are those that cause the activation of FMS-like tyrosine kinase 3 (FLT3). Therefore, FLT3 is regarded as a potential target for the treatment of AML. A novel series of thieno[2,3-d]pyrimidine-based analogs was designed and synthesized as FLT3 inhibitors. All synthesized compounds were assayed for the tyrosine kinase activity of FLT3 and growth inhibitory activity in four human leukemia cell lines (THP1, MV4-11, K562, and HL-60). Among these compounds, compound 17a, which possesses relatively short and simple substituents at the C6 position of thieno[2,3-d]pyrimidine, emerged as the most promising anti-leukemic agent. Compound 17a exhibited potent inhibition of FLT3-positive leukemic cell growth and of the FLT3 D835Y kinase; such inhibition is required for the successful treatment of AML. The data supports the further investigation of this class of compounds as potential anti-leukemic agents.
Keyword
Acute myeloid leukemia (AML)D835YFMS-like tyrosine kinase 3 (FLT3)Internal tandem duplications (ITD)Thieno[2,3-d]pyrimidine
ISSN
0223-5234
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ejmech.2014.08.001
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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