ADAM17 as a Therapeutic Target in Multiple Diseases

Authors: Arribas, Joaquin; Esselens, Cary

Source: Current Pharmaceutical Design, Volume 15, Number 20, July 2009 , pp. 2319-2335(17)

Publisher: Bentham Science Publishers

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Abstract:

As a metalloproteinase specialized in releasing membrane-tethered proteins, A Disintegrin and A Metalloproteinase 17 (ADAM17), also known as Tumor necrosis factor-α Converting Enzyme (TACE) or less commonly CD156q, has received more than its share of attention. This is mainly because major contemporary pathologies like cancer, inflammatory and vascular diseases seem to be connected to its cleavage abilities. The involvement in such a broad spectrum of diseases is due to the large variety of substrates that ADAM17 is able to cut. ADAM17 can activate growth factors or inactivate receptors by shedding their extracellular domain from the cell membrane. Similarly, it can detach cells by cleaving cell adhesion molecules. Some of these proteolytic events are part of cleavage cascades known as Regulated Intramembrane Proteolysis and lead to intracellular signaling. It is therefore clear that ADAM17 literally fulfills a key role in diverse processes and pathologies, making it a prime target for developing therapies. Here we review the role of ADAM17 in health and disease and highlight the problems to overcome for ADAM17 to mature towards a therapeutically valuable target.

Keywords: TACE; degradome; tumor; inflammation; inhibitor; shedding

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209788682398

Affiliations: 1: Medical Oncology Research Program, Vall d'Hebron University Hospital Research Institute, Psg. Vall d'Hebron 119-129, Universitat Autonoma de Barcelona (UAB), 08035 Barcelona, Spain.

Publication date: 2009-07-01

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Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

ADAM17 as a Therapeutic Target in Multiple Diseases

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