NEWS OF THE WEEK REGULATION
GERMAN REFORMS AFFECT DRUG R&D CHANGING PLANS Pfizer's R&D site in Sandwich, England, will expand as German R&D operations are consolidated.
Firms put expansions on hold because of proposed health care changes
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HARMACEUTICAL PRODUC-
ers Merck and Pfizer are changing their plans for R&D in Germany Their actions come in response to the country's proposed health care reforms that seem certain to cut into pharmaceutical companies'profits. Merck has scrapped plans to build an R&D center in Munich that would have employed
about 150 people. Pfizer will consolidate its 150-person German R&D operations, part of the Pharmacia acquisition, with its European central R&D base in Sandwich, England. Other major drugmakers are also putting on hold plans to expand R&D in Germany, the third-largest pharmaceuticals market worldwide after the U.S. andJapan. The firms are reacting to proposed German health care reforms that would nearly triple the contribution that companies have to pay insurers—from 6% of their sales on products in Germany to 16%. Under the national health
BIOCHEMISTRY
HOW CURRY COMBATS CANCER The active ingredient curcumin inhibits an enzyme that promotes tumors
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IOCHEMISTS IN SOUTH KO-
rea have discovered how curcumin fights cancer. Curcumin, the bright yellow active ingredient in turmeric (a spice used in curry), irreversibly inhibits aminopeptidase N (APN), an enzyme that spurs tumor invasiveness and angiogenesis (blood vessel growth) [Chem. Biol, 10,695 (2003)}. Scientists have known since the early 1990s that curcumin somehow slows the growth of new cancers. With further study, it was found to arrest angiogenesis. Curcumin is now in Phase I 8
C&EN / SEPTEMBER 1. 2003
clinical trials for colon cancer. Ho Jeong Kwon, professor of bioscience and biotechnology at Sejong University, Seoul, wasn't initially thinking about curcumin when he and his laboratory embarked on a large-scale chemical genetics effort to isolate antiangiogenic agents. They were looking at APN, a newly identified player in angiogenesis. APN is a membrane-bound, zinc-dependent metalloproteinase that breaks down proteins at the cell surface and helps cancer cells invade the space ofneighboring cells. Kwon's laboratory screened 3,000 mol-
care system, insurers pay for consumers'prescription drugs and get a 6% rebate from manufacturers to help contain costs; the remainder is paid by the government. Moreover, the government is proposing price caps for medicines protected by patents. Together, the actions would enable the government to chop more than SI billion from its health care budget. Walter Kobele, chairman of Pfizer Deutschland, says his company would see $160 million cut from company profits in 2004 as a result of the proposed changes. He cautions that a decrease in drug industry investment in Germany will be an unintended side effect of the legislation. "The necessity ofstructural reform is extremely urgent," Kobele says. However, "what is needed is a complete rethink—innovative drugs must finally be seen as an investment in the future ofthe patient and the system, and not as COStS."—PATRICIA SHORT
ecules for activity against APN, and curcumin showed up as a potent inhibitor. Through a combination of in vitro and in vivo enzyme assays and surface plasmon resonance analysis, Kwon and coworkers established that curcurnin's inhibition of A P N is direct and irreversible. How curcumin binds isn't known, although Kwon modeled a possible scenario. He suspects that the a, ^-unsaturated ketone moieties may covalently link to two nucleophilic amino acids in API^s active site. Hynda K Kleinman, a chemist and cell biologist at N I H who studies angiogenesis, says Kwon's finding opens up the possibility of developing more potent APN inhibitors based on the structure ofcurcumin. And curcumin itself is "an exciting compound because it can be taken orally and may not have any side effects for cancer patients."—LOUISA DALT0N HTTP://WWW.CEN-ONLINE.ORG
