Document Detail


A potent and highly efficacious Bcl-2/Bcl-xL inhibitor.
MedLine Citation:
PMID:  23448298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Our previously reported Bcl-2/Bcl-xL inhibitor, 4, effectively inhibited tumor growth but failed to achieve complete regression in vivo. We have now performed extensive modifications on its pyrrole core structure, which has culminated in the discovery of 32 (BM-1074). Compound 32 binds to Bcl-2 and Bcl-xL proteins with K(i) values of <1 nM and inhibits cancer cell growth with IC50 values of 1-2 nM in four small-cell lung cancer cell lines sensitive to potent and specific Bcl-2/Bcl-xL inhibitors. Compound 32 is capable of achieving rapid, complete, and durable tumor regression in vivo at a well-tolerated dose schedule. Compound 32 is the most potent and efficacious Bcl-2/Bcl-xL inhibitor reported to date.
Authors:
Angelo Aguilar; Haibin Zhou; Jianfang Chen; Liu Liu; Longchuan Bai; Donna McEachern; Chao-Yie Yang; Jennifer Meagher; Jeanne Stuckey; Shaomeng Wang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-03-22
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  56     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-11     Completed Date:  2013-06-11     Revised Date:  2014-04-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3048-67     Citation Subset:  IM    
Data Bank Information
Bank Name/Acc. No.:
PDB/3SP7
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cell Line, Tumor
Humans
Inhibitory Concentration 50
Mice
Mice, SCID
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
bcl-X Protein / antagonists & inhibitors*
Grant Support
ID/Acronym/Agency:
P30CA046592/CA/NCI NIH HHS; U19 CA113317/CA/NCI NIH HHS; U19CA113317/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-X Protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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