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ABSTRACT Hematopoietic malignancies frequently are characterized by defects in apoptosis signaling. This renders the malignant cells resistant to endogenous apoptotic stimuli, as well as

exogenous stimuli, such as chemotherapy drugs and radiation. The defective apoptosis seen in human cancers often results from overexpression of antiapoptotic proteins in the Bcl-2 protein

family, particularly Bcl-2 and Bcl-XL. A great deal of effort is currently aimed at developing novel agents to inhibit the expression or function of these proteins. Antisense agents directed

against Bcl-2 mRNA are showing considerable promise in clinical trials. In addition, detailed knowledge of the structures of Bcl-2 and Bcl-XL, coupled with high-throughput and

computer-assisted screening of chemical libraries, has led to the identification of a number of short peptides and small organic molecules capable of inhibiting Bcl-2 and Bcl-XL function.

These newly described agents hold considerable promise for enhancing the chemo- and radiation sensitivities of Bcl-2- and Bcl-XL-overexpressing cancers. This review will highlight recent

advances in the development and testing of agents targeting cell death inhibitors in the Bcl-2 protein family Access through your institution Buy or subscribe This is a preview of

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ADDITIONAL ACCESS OPTIONS: * Log in * Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS THE MANIPULATION OF APOPTOSIS

FOR CANCER THERAPY USING BH3-MIMETIC DRUGS Article 18 October 2021 DISCOVERY AND IDENTIFICATION OF A NOVEL SMALL MOLECULE BCL-2 INHIBITOR THAT BINDS TO THE BH4 DOMAIN Article 02 August 2022

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references AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA S Shangary & D E Johnson * Department of

Pharmacology, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA D E Johnson Authors * S Shangary View author publications You can

also search for this author inPubMed Google Scholar * D E Johnson View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shangary, S., Johnson, D. Recent advances in the development of anticancer agents targeting cell death inhibitors in the Bcl-2 protein

family. _Leukemia_ 17, 1470–1481 (2003). https://doi.org/10.1038/sj.leu.2403029 Download citation * Received: 03 March 2003 * Accepted: 14 April 2003 * Published: 29 July 2003 * Issue Date:

01 August 2003 * DOI: https://doi.org/10.1038/sj.leu.2403029 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a

shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * apoptosis * lymphoma * Bcl-2 *

Bcl-XL * BH3 domain