Online citations, reference lists, and bibliographies.
← Back to Search

Bcl-2 Family Proteins As Targets For Anticancer Drug Design

Z. Huang
Published 2000 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Bcl-2 family proteins are key regulators of programmed cell death or apoptosis that is implicated in many human diseases, particularly cancer. In recent years, they have attracted intensive interest in both basic research to understand the fundamental principles of cell survival and cell death and drug discovery to develop a new class of anticancer agents. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions in either inhibiting or promoting cell death. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL commonly found in human cancers contributes to neoplastic cell expansion and interferes with the therapeutic action of many chemotherapeutic drugs. The functional blockade of Bcl-2 or Bcl-xL could either restore the apoptotic process in tumor cells or sensitize these tumors for chemo- and radiotherapies. This article reviews the recent progress in the design and discovery of small molecules that block the anti-apoptotic function of Bcl-2 or Bcl-xL. These chemical inhibitors are effective modulators of apoptosis and promising leads for the further development of new anticancer agents.
This paper references
10.1016/S0040-4039(00)01195-3
Reactions of salicylaldehydes with alkyl cyanoacetates on the surface of solid catalysts: syntheses of 4H-chromene derivatives
N. Yu (2000)
10.1016/0005-2728(94)90241-0
Structural factors of antimycin A molecule required for inhibitory action.
N. Tokutake (1994)
Mol
A Kelekar (1997)
Biochim
N Tokutake (1994)
10.1038/369321A0
BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
X. Yin (1994)
10.1074/jbc.274.19.13298
Bak BH3 Peptides Antagonize Bcl-xL Function and Induce Apoptosis through Cytochrome c-independent Activation of Caspases*
E. P. Holinger (1999)
10.1073/PNAS.95.25.14681
Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria.
M. Narita (1998)
10.1016/S0092-8674(00)80572-3
Solution Structure of BID, an Intracellular Amplifier of Apoptotic Signaling
J. Chou (1999)
10.1128/MCB.17.12.7040
Bad is a BH3 domain-containing protein that forms an inactivating dimer with Bcl-XL.
A. Kelekar (1997)
10.1126/SCIENCE.281.5381.1322
The Bcl-2 protein family: arbiters of cell survival.
J. Adams (1998)
10.1038/381335A0
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death
S. Muchmore (1996)
Curr
S Cosulich (1997)
10.1016/S0960-9822(06)00410-6
Regulation of apoptosis by BH3 domains in a cell-free system
S. Cosulich (1997)
10.1073/PNAS.95.9.4997
Bax directly induces release of cytochrome c from isolated mitochondria.
J. Jürgensmeier (1998)
10.1054/DRUP.2000.0123
Molecular targets and cancer therapeutics: discovery, development and clinical validation.
B. Teicher (2000)
10.1126/science.7878464
Apoptosis in the pathogenesis and treatment of disease
C. Thompson (1995)
Proc
J Wang (2000)
Proc
JM Jurgensmeier (1998)
10.1016/S0163-7258(00)00052-8
Structural chemistry and therapeutic intervention of protein-protein interactions in immune response, human immunodeficiency virus entry, and apoptosis.
Z. Huang (2000)
Annu
D Chao (1998)
10.1126/SCIENCE.275.5302.983
Structure of Bcl-xL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis
M. Sattler (1997)
10.1002/(SICI)1097-4644(19960101)60:1<23::AID-JCB5>3.0.CO;2-5
BCL‐2 family proteins: Regulators of cell death involved in the pathogenesis of cancer and resistance to therapy
John Calvin Reed (1996)
91st Ann
BA Morgan (2000)
10.1074/jbc.272.17.11350
A Common Binding Site Mediates Heterodimerization and Homodimerization of Bcl-2 Family Members*
J. L. Díaz (1997)
10.1074/jbc.272.44.27886
Crystal Structure of Rat Bcl-xL
M. Aritomi (1997)
Modulation of Bcl-2 protein levels by an intracellular anti-Bcl-2 single-chain antibody increases drug-induced cytotoxicity in the breast cancer cell line MCF-7.
A. Piché (1998)
Pharmacol
Z. Huang (2000)
10.1146/ANNUREV.IMMUNOL.16.1.395
BCL-2 family: regulators of cell death.
D. Chao (1998)
10.1016/S0140-6736(96)11103-X
BCL-2 antisense therapy in patients with non-Hodgkin lymphoma
A. Webb (1997)
10.1083/JCB.124.1.1
Bcl-2 and the regulation of programmed cell death
J. C. Reed (1994)
10.1016/S0092-8674(00)80573-5
Solution Structure of the Proapoptotic Molecule BID A Structural Basis for Apoptotic Agonists and Antagonists
J. McDonnell (1999)
10.1073/PNAS.97.13.7124
Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.
J. L. Wang (2000)
10.7164/ANTIBIOTICS.33.668
Novel antitumor antibiotics, tetrocarcins.
F. Tomita (1980)
10.1038/NM0298-232
bcl-2 antisense therapy chemosensitizes human melanoma in SCID mice
Burkhard Jansen (1998)
10.1074/JBC.271.13.7440
Proapoptotic Protein Bax Heterodimerizes with Bcl-2 and Homodimerizes with Bax via a Novel Domain (BH3) Distinct from BH1 and BH2 (*)
H. Zha (1996)
10.1002/j.1460-2075.1995.tb00246.x
A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions.
T. Chittenden (1995)
10.1074/jbc.272.49.30866
Dimerization Properties of Human BAD
S. Ottilie (1997)
10.1515/9783111576855-015
J
Seguin Hen (1824)
Proc
M Narita (1998)



This paper is referenced by
10.1016/S0065-7743(02)37013-1
Chapter 12. Intracellular signaling targets for cancer chemosensitization
T. Gesner (2002)
10.5772/39284
Genomics of Basal and Squamous Cell Carcinomas
V. Samarasinghe (2012)
10.1186/1476-4598-7-90
Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells
Yekaterina Y. Zaytseva (2008)
10.1093/bioinformatics/18.1.67
Discrete simulation of regulatory homo- and heterodimerization in the apoptosis effector phase
C. Siehs (2002)
Influence of covalently conjugated monodisperse polyethylene glycol chains on in vitro properties ofsiRNA oligonucleotides
Zuzana Gaziova (2013)
nanoparticles loaded with cisplatin on sKOV3/DDP ovarian carcinoma cells
Z. Jiang (2009)
10.1007/s00280-004-0944-5
Targeting BCL-2 overexpression in various human malignancies through NF-κB inhibition by the proteasome inhibitor bortezomib
B. Fahy (2004)
10.3892/or.2011.1543
Partial sensitization of human bladder cancer cells to a gene-therapeutic adenovirus carrying REIC/Dkk-3 by downregulation of BRPK/PINK1.
Yu Jin (2012)
10.1517/13543776.2011.638285
Nuclear factor-kappa B inhibitors; a patent review (2006 – 2010)
Jae-Hwan Kwak (2011)
The effect of histone deacetylase inhibitors on SRC and BCL2L1 gene expression and a potential role for phosphatases in their transcriptional repression
Stacy Chapman (2013)
10.1016/J.CANLET.2005.03.029
Conjugated linoleic acid induces apoptosis in MDA-MB-231 breast cancer cells through ERK/MAPK signalling and mitochondrial pathway.
A. Miglietta (2006)
Comparison between Platinum-Azidothymidine and Azidothymidine Effects on Bcl-2 and Telomerase Gene Expression in Rats with Hepatocellular Carcinoma
Abdolreza Sabokrouh (2015)
10.1074/jbc.M502364200
TrkA Induces Apoptosis of Neuroblastoma Cells and Does So via a p53-dependent Mechanism*[boxs]
J. Lavoie (2005)
10.1593/NEO.05691
(-)-gossypol inhibits growth and promotes apoptosis of human head and neck squamous cell carcinoma in vivo.
K. G. Wolter (2006)
BCL-2 family function in antiestrogen-resistant breast cancer cells
A. Crawford (2009)
10.1016/j.biocel.2013.01.013
The Bcl-2/Bcl-xL inhibitor BH3I-2' affects the dynamics and subcellular localization of sumoylated proteins.
Mélodie B. Plourde (2013)
10.1038/sj.onc.1207102
The Bcl-2 family: roles in cell survival and oncogenesis
S. Cory (2003)
10.1677/JOE.0.1780265
Prolactin regulation of Bcl-2 family members: increased expression of bcl-xL but not mcl-1 or bad in Nb2-T cells.
S. K. Kochendoerfer (2003)
10.1053/j.gastro.2009.10.050
Reg IV regulates normal intestinal and colorectal cancer cell susceptibility to radiation-induced apoptosis.
K. Bishnupuri (2010)
10.5772/55817
Pathways of Intrinsic Apoptosis in Neuroblastoma: Targets for Therapeutics and New Drug Development
Fieke Lamers (2013)
10.1038/sj.jid.5701243
Superficial, nodular, and morpheiform basal-cell carcinomas exhibit distinct gene expression profiles.
M. Yu (2008)
Inactivation of NFK B by 3 , 3 ¶-diindolylmethane contributes to increased apoptosis induced by chemotherapeutic agent in breast cancer cells
K. Rahman (2007)
10.1177/154411130201300502
The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy.
S. Sonis (2002)
10.1117/12.524539
Effects of the bile acid UDCA on PDT efficacy in vitro and in vivo
David Kessel (2004)
10.7150/IJBS.7.805
MicroRNA-7 Inhibits the Growth of Human Non-Small Cell Lung Cancer A549 Cells through Targeting BCL-2
S. Xiong (2011)
10.1021/MP050065E
HPMA copolymer-bound doxorubicin induces apoptosis in ovarian carcinoma cells by the disruption of mitochondrial function.
A. Malugin (2006)
10.2217/nnm.12.73
Efficient systemic delivery of siRNA by using high-density lipoprotein-mimicking peptide lipid nanoparticles.
Qiaoya Lin (2012)
10.4161/cc.8.23.10114
Differential scanning fluorimetry as secondary screening platform for small molecule inhibitors of Bcl-XL
K. F. Wan (2009)
10.1016/J.YEXCR.2004.02.005
The small leucine-rich proteoglycan lumican inhibits melanoma progression.
B. Vuillermoz (2004)
10.1016/j.bbrc.2009.02.012
bFGF rescues imatinib/STI571-induced apoptosis of sis-NIH3T3 fibroblasts.
M. Ohshima (2009)
10.1016/j.ccr.2012.12.001
NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers.
W. Zhou (2013)
10.22246/JIKM.2018.39.1.44
Review of Domestic Research on Traditional Korean Medicine for Breast Cancer
Gajin Han (2018)
See more
Semantic Scholar Logo Some data provided by SemanticScholar