Abstract:
:Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridine-based, irreversible BTK inhibitors were reported with IC50 values ranging from 1.9 to 236.6 nM in the enzymatic inhibition assay. Compounds 6 and 7 significantly inhibited the proliferation of Ramos cells which overexpress the BTK enzyme, as well as the autophosphorylation of BTK at Tyr223 and the activation of its downstream signaling molecule PLCγ2. Overall, this series of compounds could provide a promising starting point for further development of potent BTK inhibitors for B-cell malignancy treatment.
journal_name
Medchemcommjournal_title
MedChemCommauthors
Chen H,Song P,Diao Y,Hao Y,Dou D,Wang W,Fang X,Wang Y,Zhao Z,Ding J,Li H,Xie H,Xu Ydoi
10.1039/c8md00019ksubject
Has Abstractpub_date
2018-03-13 00:00:00pages
697-704issue
4eissn
2040-2503issn
2040-2511pii
c8md00019kjournal_volume
9pub_type
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