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Last updated on February 13, 2012 at 17:08 EST

Drug Developers Have Yet to Bring Apoptosis Drugs to the Market

March 23, 2006

Research and Markets (http://www.researchandmarkets.com/reports/c32152) has announced the addition of Discoveries and Challenges in Early-Stage Apoptosis Drug Development to their offering.

Business Implications

— Apoptosis is the major pathway of programmed cell death, or regulated cellular autodestruction, in which individual cells commit suicide. As a result of its role in cell development, the immune system, and protection against mutations and cancer, it has been an interesting target for drug developers since the early 1990s; however, no apoptosis drugs have yet reached the market.

— Most of the activity in the development of apoptosis drugs has centered on apoptosis inducers for the treatment of cancer. This work has been hampered by the fact that most targets are “undruggable” protein-protein interactions. To circumvent the problem, researchers have focused on the development of antisense drugs. The antisense drug nearest to market is oblimersen (Genta’s Genasense), a first-generation drug being submitted for approval in the United States and Europe.

— Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is of particular interest to oncology drug developers because it has been found to selectively induce apoptosis in cancer cells independent of p53, which is usually inactivated in human cancers. Evidence suggests that TRAIL may be involved in tumor surveillance by natural killer cells and in defense against viral infection.

— Caspases are a class of proteases that constitute a key component of apoptotic pathways. The development of caspase inhibitors as therapeutics for conditions characterized by excessive apoptosis has been hampered by the existence of alternative pathways of cell death, which have only recently been elucidated. However, Idun, which was recently acquired by Pfizer, has an apoptosis inhibitor, IDN-6556, in Phase II clinical trials for liver disease, a condition in which these alternative pathways are not an issue.

Apoptosis, the major and best-studied pathway of programmed cell death, plays an important role in embryonic development, the immune system, and protection against mutations and cancer. As such, it has become an intriguing focus of investigation among pharmaceutical companies seeking to treat illnesses ranging from cancer to cirrhosis.

In this Decision Resources report, we explain the apoptotic process, discuss several proteins within the apoptotic pathways that may represent potential targets for drug development, describe apoptosis modulators and inhibitors in development, and analyze the challenges associated with developing agents that target this pathway, especially those associated with caspase inhibitors

Topics Covered

Introduction

An Overview of Apoptosis

Characteristics of Apoptosis

Detecting Apoptosis

Role of Apoptosis in Human Development

Role of Apoptosis in Disease

The Apoptotic Pathways

Apoptosis Activators in Development for Cancer6

Bcl-2 Inhibitors

IAP Inhibitors

TRAIL Receptor Agonists

Other Intrinsic Pathway

Drug Discovery Methods

Caspase Inhibitors as Antiapoptotic Agents

Challenges to Caspase Inhibitor Development

IDN-6556

Outlook

Figure 1. Diagram of Central Apoptosis Pathways

Figure 2. Schematic of Pathways for Caspase-Independent Cell Death

Table 1. Leading Apoptosis Activators in Clinical Trials for the Treatment of Cancer

Table 2. Problems and Potential Solutions in Developing Apoptosis-Based Drugs

Companies mentioned in this report include:

— Genta

— Ascenta Therapeutics

— Gemin X

— Aegera Therapeutics

— Avi BioPharma

— Isis/Eli Lilly

— Human Genome Sciences/GlaxoSmithKline

— Genentech/Amgen

— Pfizer

— Idun

For more information visit http://www.researchandmarkets.com/reports/c32152