Abstract:
:A class of compounds with a common thiazolo[3,2-a]pyrimidinone motif has been developed as general inhibitors of Bcl-2 family proteins. The lead compound was originally identified in a random screening of a small compound library using a fluorescence polarization-based competitive binding assay. Its binding to the Bcl-x(L) protein was further confirmed by (15) N-HSQC NMR experiments. Structural modifications on the lead compound were guided by the outcomes of molecular modeling studies. Among the 42 compounds obtained, a number of them exhibited much improved binding affinities to Bcl-2 family proteins as compared to the lead compound. The most potent compound, BCL-LZH-40, inhibited the binding of BH3 peptides to Bcl-x(L), Bcl-2, and Mcl-1 with inhibition constants (K(i)) of 17, 534, and 200 nM, respectively.
journal_name
ChemMedChemjournal_title
ChemMedChemauthors
Zhou B,Li X,Li Y,Xu Y,Zhang Z,Zhou M,Zhang X,Liu Z,Zhou J,Cao C,Yu B,Wang Rdoi
10.1002/cmdc.201000484subject
Has Abstractpub_date
2011-05-02 00:00:00pages
904-21issue
5eissn
1860-7179issn
1860-7187journal_volume
6pub_type
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