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PMID: 17921043 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

BH3 mimetics to improve cancer therapy; mechanisms and examples.

Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy ·Vol. 10 ·No. 6 ·2007-12-00 ·Pages 207-17

Zhang L, Ming L, Yu J

Abstract

Tumor cell survival is highly dependent on the expression of certain pro-survival Bcl-2 family proteins. An attractive therapeutic approach is to inhibit these proteins using agents that mimic the Bcl-2 homology 3 (BH3) domains of the proapoptotic Bcl-2 family members, which neutralize these proteins by binding to their surface hydrophobic grooves. A number of BH3 mimetic peptides and small molecules have been described, a few of which have advanced into clinical trials. Recent studies have highlighted ABT-737, a bona fide BH3 mimetic and potent inhibitor of antiapoptotic Bcl-2 family members, as a promising anticancer agent. This review summarizes recent advances in understanding the mechanisms of action of BH3 domains and several classes of BH3 mimetics, as well as the prospects of using these agents to improve cancer therapy.

MeSH Terms
Amino Acid Sequence Animals Antineoplastic Agents/pharmacology,therapeutic use Apoptosis/drug effects Biphenyl Compounds/pharmacology,therapeutic use Drug Resistance, Neoplasm Drugs, Investigational/pharmacology,therapeutic use Humans Molecular Sequence Data Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins/metabolism Neoplasms/drug therapy,metabolism,pathology Nitrophenols/pharmacology,therapeutic use Piperazines/pharmacology,therapeutic use Protein Structure, Tertiary Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors,chemistry,metabolism Sequence Alignment Sulfonamides/pharmacology,therapeutic use Treatment Outcome bcl-X Protein/antagonists & inhibitors,metabolism
Chemicals
ABT-737 Antineoplastic Agents Biphenyl Compounds Drugs, Investigational Myeloid Cell Leukemia Sequence 1 Protein Neoplasm Proteins Nitrophenols Piperazines Proto-Oncogene Proteins c-bcl-2 Sulfonamides bcl-X Protein
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhang Lin
University of Pittsburgh Cancer Institute, Departments of Pharmacology and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. zhanglx@upmc.edu
Ming Lihua
Yu Jian
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Article Info
Journal
Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Abbr.
Drug Resist Updat
ISSN
1532-2084
DOI
10.1016/j.drup.2007.08.002
Email
zhanglx@upmc.edu
Published
2007-12-00
Epub
2007-00-24
Pages
207-17
Language
English
Region
Scotland
NLM ID
9815369
PMCID
PMC2265791
Subset
IM
Grants
NCI NIH HHS · R01 CA106348-03 · United States
NCI NIH HHS · CA121105 · United States
NCI NIH HHS · R01 CA121105-01A1 · United States
NCI NIH HHS · R01 CA121105 · United States
NCI NIH HHS · R01 CA106348-01 · United States
NCI NIH HHS · R01 CA106348-02 · United States
NCI NIH HHS · CA106348 · United States
NCI NIH HHS · R01 CA106348 · United States
NCI NIH HHS · R01 CA106348-04 · United States
External Links
PubMed source DOI: 10.1016/j.drup.2007.08.002 PMC Full Text View journal details
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