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448 Part Three Key System Applications for the Digital Age

structure-based design helped. Reseachers led by Dr. Jean Cui at the biotech firm
Sugen were trying to block a protein called c-Met that was found to play an impor-
tant role in the growth of cancer tumors. The researchers identified a naturally
occurring molecule that connected to c-Met, but the molecule at that stage lacked
properties, such as avoiding rapid metabolism in the body, that would make it a
workable drug. Other researchers using structure-based design crystallized the
c-Met protein with one of the potential drug molecules linked to it, subjected this
arrangement to X-rays, and used computer analysis to deduce the structure of the
protein and how the prototype drug molecule “key” fit into its “lock.”
Dr. Cui was able to use this information to develop an entirely new molecule
that could both bind to c-Met and that had properties suitable for a drug. Colleagues
used Cui’s sketch of what she thought the drug design should look like to model
compounds virtually on a computer and make them in test tubes for further
study. By February 2003, animal tests showed that the molecule could arrest
tumor growth. After Sugen and its parent company Pharmacia were acquired by
Pfizer, researchers further refined the molecule to make Xalkori ready for testing
in humans. Xalkori was approved by the FDA in the summer of 2011.
In addition to treating lung cancer, Xalkori is being used in conjunction with an
Alzheimer’s disease treatment developed by Eli Lilly & Co., an antibiotic made
by GlaxoSmithKline PLC that is in clinical trials, and a Sanofi SA blood thinner
that is in the final stages of development. Vertex’s hepatitis C therapy, called
Incivek, was FDA-approved in May 2011, and its drug for treating cystic fibrosis,
called Ivacaftor, was approved in January 2012.
Sources: Jonathan D. Rockoff, “Drug Discovery Gets an Upgrade,” The Wall Street Journal, April
16, 2012; www.vrtx.com, accessed July 1, 2012; and Matthew Herperi, “Pfizer Wins Approval
For Xalkori, Lung Cancer Drug That Heralds Age Of Expensive, Personalized Medicines,”
Forbes, August 26, 2011.
he experience of the medical researchers engaged in drug discovery
Tdescribed in this case shows how business performance can benefit
by using technology to facilitate the acquisition and application of knowl-
edge. Facilitating access to knowledge, improving the quality and currency of
knowledge, and using that knowledge to improve business processes are vital to
success and survival in all areas of business as well as in medical research.
The chapter-opening diagram calls attention to important points raised by this
case and this chapter. Phamaceutical companies trying to develop new drugs
are very challenged because the drug discovery process is so painstaking and
complicated. Earlier methods were not very accurate or effective and depended
too much on trial and error. This is beginning to change, thanks to the develop-
ment of new processes for visualizing and designing new drugs and the use of
powerful computers and information technology.
Drug researchers using structure-based design benefit from a new process of
visualizing and modeling promising compounds at the molecular level. Powerful
computers for analyzing molecular structure, databases organizing data about
specific molecules and compounds, and software for visualizing and modeling
molecules all play a role in creating new knowledge and making that knowledge
available to researchers. Thanks to better systems for capturing and creat-
ing knowledge, drug researchers and pharmaceutical companies have a much
more accurate and efficient process for developing effective medications and for
understanding how these drugs actually work.
Here are some questions to think about: Why are computers so important
in drug discovery? What roles are played by computers in the drug discovery
process?

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