Abbott And Idun To Develop Apoptosis Cancer Drugs
Abbott Laboratories (Abbott Park, IL) and Idun Pharmaceuticals, Inc. (La Jolla, CA) have announced a worldwide research and development agreement to focus on the discovery and development of apoptosis drugs for treating cancer. The proposed products will regulate the activity of selected proteins involved in the cell pathway leading to programmed cell death, or apoptosis. This strategic initiative combines proprietary technologies from both Abbott and Idun in a major new discovery effort to identify small molecule drugs that kill tumor cells by specifically targeting the apoptotic pathway. Under terms of the agreement, Abbott has committed $30 million, which includes an equity investment and research funding. Idun will receive milestone payments and royalties on products resulting from the research program.
Idun is responsible for developing primary molecular assays against targets in the core of the apoptosis pathway. These assays will be used by Abbott for high-throughput screening of compound libraries and compound analysis using Abbott's proprietary SAR by NMR technology. Secondary characterization of compound activity will be carried out at Idun using Idun's battery of biological apoptosis assays.
SAR by NMR was developed at Abbott and uses nuclear magnetic resonance spectroscopy to screen a defined library of diverse small molecules for their ability to bind to the individual pockets of a protein drug target. This technique has been shown to significantly speed the difficult, time-consuming process for identifying molecules that bind to important protein drug targets.
Abbott holds exclusive worldwide rights for compounds resulting from the collaboration that move forward into human clinical testing. Abbott is also responsible for preclinical and clinical development of any drug leads emerging from the joint program and for government approval, manufacturing, marketing and sales.
Drug companies can exploit apoptosis in two ways: by enhancing (for cancer) or inhibiting it (for degenerative diseases). Privately held Idun is doing both. In a separate agreement with Novartis, Ltd., Idun is developing drugs that inhibit apoptosis in the brain associated with CNS disease. Additional discovery programs at Idun are aimed at the development of novel drugs to protect or minimize cell damage resulting from obstructed blood flow (ischemia) or other insults to key organs such as the heart and liver.
About Apoptosis
Cell death, once believed to be a passive non-specific event, is now known to be an active biochemical process. All cells have the capacity to die by this process, called programmed cell death or apoptosis. Many important human diseases are caused by abnormalities in the control of apoptosis. These abnormalities can result in either a pathological increase in cell number (e.g. cancer) or a damaging loss of cells (e.g. degenerative diseases). Recent data indicate that cells have a discrete cell death pathway defined by a specific set of genes. These genes encode proteins that form the biochemical cascade that ultimately leads to cell death.
The key genes that control the cell death process are the cell death effectors of the CED-3/ICE ("caspase") family and the cell death inhibitors of the Bcl-2 family. The caspase gene family encodes a set of proteases responsible for carrying out the death process. In a living cell, these proteases are normally kept inactive by proteins encoded by the Bcl-2 family. Small molecule drugs that specifically modulate the activity of the caspase family, the Bcl-2 family, or other key points in the apoptotic pathway, exert control over cell death and have utility in diseases characterized by either excessive or insufficient levels of apoptosis.
Supporting each of Idun's drug discovery programs is a set of molecular and cellular tools for monitoring apoptosis in cells and animals, and for evaluating the effects of candidate drug molecules on the cell death process. These systems allow compounds to be evaluated in naive cells or in cells stressed to mimic in vivo disease conditions (e.g., ischemia, cytokine treatment, irradiation, etc.). Idun has developed rapid, quantitative assays to assess the effects of apoptosis on multiple cellular compartments, including cytoplasmic, nuclear and membrane markers, using a combination of enzymological and biochemical readouts. These methods have been applied to diverse cell types, including neurons, lymphocytes, cardiac myocytes, and several epithelial cancers. In addition, Idun has created an advanced relational database that contains both biological and chemical data, facilitating the rapid identification of correlation between chemical structures and pro-apoptotic or anti-apoptotic function.
For more information: Steven Mento, CEO, Idun Pharmaceuticals, 11085 North Torrey Pines Road, Suite 300, La Jolla, CA 92037. Tel: 619-623-1330. Fax: 619-623-2765.