Researchers at Merck KGaA and the Massachusetts General Hospital Win
The World-Wide Race for the First Full Structure of Integrin alpha-v-beta-3,
One of the Most Exciting Target Molecules in Today's Pharma Research
DARMSTADT, Germany, and BOSTON, Sept. 6 /PRNewswire/ -- After five years
of transatlantic collaboration, researchers of Merck KGaA and the
Massachusetts General Hospital (MGH) have solved, for the first time ever, the
full structure of an integrin receptor. This key protein plays a major role
in the control of biological processes and diseases, ranging from cancer to
restenosis, osteoporosis, rheumatism and inflammation. The important findings
of the research team, which will appear in Science Magazine, were published
today on the Science Express website (http://www.scienceexpress.org) .
"This is the first look anyone has had at the whole structure of an
integrin, and it reveals wholly unexpected aspects that may lead to innovative
therapeutics," said Dr. Inge Lues, Vice President, Preclinical R&D at Merck
KGaA. "This scientific breakthrough is a result of our strong commitment to
cutting edge research in Oncology, and international collaborations with World
Class Investigators," Lues added.
"Knowing the shape of this receptor will help us all develop new
strategies to target many serious diseases," says M. Amin Arnaout, MD,
Director of the Structural Biology Program at MGH and Chief of the MGH Renal
Unit. The MGH team of researchers, headed by Dr. Anaout, has been trying to
decipher the three dimensional structure of this particular integrin receptor
for several years.
Integrin receptors transmit chemical signals from a cell's surface into
its interior, which regulate most cellular processes such as attachment,
proliferation, differentiation, and survival. Integrin alpha-v-beta-3, for
which the full structure now has been resolved, is one of the therapeutically
most exiting members of this receptor family.
In a novel therapeutic approach to fight cancer, Merck KGaA researchers
try to specifically block this integrin receptor which is located on the
surface of endothelial cells. Solid tumors activate these cells to promote
the sprouting of new blood vessels that connect the tumor to the main
circulating system. This process, which enables the tumor to grow and
metastasise, can be blocked by a specific integrin inhibitor called
Cilengitide. This new drug candidate, now in Phase II clinical trials, binds
specifically to an integrin, resulting in death of activated endothelial
cells, reduced blood vessel formation within the tumor and ultimately
inhibition of tumor growth and metastasis.
"The better you know the precise shape of the binding site of the
integrin, the better you are able to design specific inhibitors, which may
result in novel drugs," said Merck KGaA researcher Dr. Simon L. Goodman, who,
together with Dr. Reinhardt Dunker and Dr. Beate Diefenbach, succeeded in
producing gram amounts of the receptor molecule at an ultra high purity level
by applying recombinant cDNA technology. This was the essential prerequisite
for the MGH scientists to generate crystals of the integrin receptor in
sufficient quality. By the end of 2000, in a very competitive field, they
finally solved the full structure of the receptor by X-ray crystallography.
Note:
Please visit the Media/Investor Relations section of the Merck KGaA
website (http://www.merck.de) to download a picture of the integrin receptor
molecule.
The Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH conducts the
largest hospital-based research program in the United States, with an annual
research budget of more than $300 million and major research centers in AIDS,
the neurosciences, cardiovascular research, cancer, cutaneous biology, kidney
and vascular biology research, photo-medicine, transplantation biology and
structural biology.
Headquartered in Darmstadt/Germany, the Merck Group generated sales of
EUR 6.7 billion in 2000 in the fields of Pharmaceuticals, Specialty Chemicals,
Lab Products and Lab Distribution. Founded in 1668, the Merck Group is
represented today by more than 200 companies in 52 countries and employs
34,400 people world-wide. The company groups its operating activities under
Merck KGaA, in which E. Merck, as a general partner, holds the Merck family's
74 percent equity interest in Merck KGaA. The Merck Group strongly believes
that promotion of its employees' self-initiative and self-responsibility,
application-oriented research and development and close customer relationships
in the markets are the keys to long-term corporate success.
SOURCE Merck KGaA
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Related links:
http://www.scienceexpress.org
http://www.merck.de
CONTACT:
Dr. Hartmut Vennen of Merck,
+49-6151-72-2386, or fax, +49-6151-72-7707, or
hartmut.vennen@merck.de
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