Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents

B.D. Zeitlin, I.J. Zeitlin, J.E. Nor, National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder)

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis and obtain a survival advantage through aberrant expression of Bcl-2. The new and remarkably diverse class of drugs, small-molecule inhibitors of Bcl-2 (molecular weight approximately 400 to 800 Daltons), is examined herein. We present the activities of these compounds along with clinical observations, where available. The effects of Bcl-2 inhibition on attenuation of tumor cell growth are discussed, as are studies revealing the potential for Bcl-2 inhibitors as antiangiogenic agents. Despite an enormous body of work published for the Bcl-2 family of proteins, we are still learning exactly how this group of molecules interacts and indeed what they do. The small-molecule inhibitors of Bcl-2, in addition to their therapeutic potential, are proving to be an important investigative tool for understanding the function of Bcl-2. (Abstract from: http://jco.ascopubs.org/cgi/content/abstract/26/25/4180)
LanguageEnglish
Pages4180-4188
Number of pages9
JournalJournal of Clinical Oncology
Volume26
Issue number25
DOIs
Publication statusPublished - 1 Sep 2008

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Angiogenesis Inhibitors
Antineoplastic Agents
Pharmaceutical Preparations
Apoptosis
Neoplasms
Proteins
Molecular Weight
Inhibition (Psychology)
Learning
Ligands
Growth

Keywords

  • tea polyphenol epigallocatechin- 3-gallate
  • colon carcinoma cells
  • breast cancer
  • chronic lymphocytic- leukemia
  • green tea
  • prostrate cancer cells

Cite this

Zeitlin, B. D., Zeitlin, I. J., Nor, J. E., & National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder) (2008). Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents. Journal of Clinical Oncology, 26(25), 4180-4188. https://doi.org/10.1200/JCO.2007.15.7693
Zeitlin, B.D. ; Zeitlin, I.J. ; Nor, J.E. ; National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder). / Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 25. pp. 4180-4188.
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Zeitlin, BD, Zeitlin, IJ, Nor, JE & National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder) 2008, 'Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents' Journal of Clinical Oncology, vol. 26, no. 25, pp. 4180-4188. https://doi.org/10.1200/JCO.2007.15.7693

Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents. / Zeitlin, B.D.; Zeitlin, I.J.; Nor, J.E.; National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder).

In: Journal of Clinical Oncology, Vol. 26, No. 25, 01.09.2008, p. 4180-4188.

Research output: Contribution to journalArticle

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AU - Zeitlin, B.D.

AU - Zeitlin, I.J.

AU - Nor, J.E.

AU - National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder)

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AB - The specific targeting of diseases, particularly cancer, is a primary aim in drug development, as specificity reduces unwelcome effects on healthy tissue and increases drug efficacy at the target site. Drug specificity can be increased by improving the delivery system or by selecting drugs with affinity for a molecular ligand specific to the disease state. The role of the prosurvival Bcl-2 protein in maintaining the normal balance between apoptosis and cellular survival has been recognized for more than a decade. Bcl-2 is vital during development, much less so in adults. It has also been noted that some cancers evade apoptosis and obtain a survival advantage through aberrant expression of Bcl-2. The new and remarkably diverse class of drugs, small-molecule inhibitors of Bcl-2 (molecular weight approximately 400 to 800 Daltons), is examined herein. We present the activities of these compounds along with clinical observations, where available. The effects of Bcl-2 inhibition on attenuation of tumor cell growth are discussed, as are studies revealing the potential for Bcl-2 inhibitors as antiangiogenic agents. Despite an enormous body of work published for the Bcl-2 family of proteins, we are still learning exactly how this group of molecules interacts and indeed what they do. The small-molecule inhibitors of Bcl-2, in addition to their therapeutic potential, are proving to be an important investigative tool for understanding the function of Bcl-2. (Abstract from: http://jco.ascopubs.org/cgi/content/abstract/26/25/4180)

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KW - colon carcinoma cells

KW - breast cancer

KW - chronic lymphocytic- leukemia

KW - green tea

KW - prostrate cancer cells

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Zeitlin BD, Zeitlin IJ, Nor JE, National Institutes of Health/National Institute of Dental and Craniofacial Research (Funder). Expanding circle of inhibition: small-molecule inhibitors of bcl-2 as anticancer cell and antiangiogenic agents. Journal of Clinical Oncology. 2008 Sep 1;26(25):4180-4188. https://doi.org/10.1200/JCO.2007.15.7693