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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/11211
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| Title: | Optimization of furanopyrimidine-based kinase inhibitors: Identification of a BTK kinase inhibitor for the treatment of B cell lymphoma |
| Authors: | Wang, WC;Hsu, YC;Shiao, HY;Hung, HC;Kuo, CC;Lee, JC;Hsu, TA;Hsieh, HP |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research |
| Abstract: | According to the statistics from Ministry of Health and Welfare in Taiwan, non-Hodgkin's lymphoma is ranked as number nine on leading cause of cancer death toward both male and female people. In Taiwan, 85% non-Hodgkin's lymphoma patients belong to B cell lymphoma patients. In general, these kinds of blood diseases were treated by traditional chemotherapy or radiation therapy, but the results exert poor treatment effectiveness. In these years, scientists reported Bruton’s tyrosine kinase (BTK) is a key component in the B-cell receptor signal pathway regulating survival, activation, proliferation, and differentiation of B cells. Several studies demonstrated that BTK is overexpressed in several B cell lymphomas and BTK inhibitors may be useful in lymphoma patients. Hence, BTK inhibitors may constitute an exciting new generation of treatments for B cell lymphomas. In our effort to develop novel BTK inhibitors, BPRBK0005 was first identified as a BTK lead through screening our in house synthesized kinase inhibitors. We next sought in silico means to proceed further lead optimizations. A new series of furanopyrimidinecontaining derivatives were synthesized and evaluated against BTK enzyme- and cellbased assays. Among these, BPRBK0169 reveal excellent BTK inhibition with an IC50 value of 10 nM, calcium flux inhibition with an IC50 value of 11 nM, as well as up to 38-fold more potent antiproliferation in Ramos lymphoma cell line than the leading clinical drug, ibrutinib. Accordingly, it is considered a highly promising candidate for further development. |
| Date: | 2015-08 |
| Relation: | Abstracts of Papers of the American Chemical Society. 2015 Aug;250:Meeting Abstract 180. |
| Link to: | https://www.acs.org/content/acs/en/meetings/national-meeting/about/meetings-archive.html |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000432475701334 |
| Appears in Collections: | [謝興邦] 會議論文/會議摘要
[李靜琪] 會議論文/會議摘要
[郭靜娟] 會議論文/會議摘要
[王文傑] 會議論文/會議摘要
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| ISI000432475701334.pdf | 89Kb | Adobe PDF | 1113 | View/Open |
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