This December 1996 Press Release by Abbott explains SAR by NMR:
ABBOTT SCIENTISTS DEVELOP REVOLUTIONARY DRUG DISCOVERY
TECHNIQUE
SAR by NMR May Speed Discovery, Multiply New Therapies
Abbott Park, IL. - December 13, 1996 - A team of scientists at Abbott Laboratories has developed a
revolutionary technique for discovering new drugs which may have far-reaching implications for disease
management. Called SAR by NMR (Structure-Activity Relationships by Nuclear Magnetic Resonance),
the technique has been shown to significantly speed the difficult and time-consuming process for
identifying molecules that bind to important protein drug targets. Identifying these "active" molecules
(those that bind) is the essential first step in developing an effective drug. Results of this team's work
recentIy were reported in Science magazine [Science 274, I531 (1996).
The process of discovering drugs is akin to seeking the needle in the haystack. The traditional
screening of chemical libraries is a slow process requiring scientists to analyze hundreds of
thousands of molecules to identify active compounds. The SAR by NMR method can dramatically
shorten this process.
"SAR by NMR 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," explains Dr.
Stephen Fesik, the inventor of the technique and leader of the team that demonstrated its
effectiveness. "Once two molecules are identified that bind to nearby sites on the protein, these two
compounds are linked together to produce a molecule that binds even more tightly, which makes it
more effective in altering the abnormal activity of that protein."
Fesik notes the comparison of SAR by NMR to combinatorial chemistry, one of today's most
advanced drug discovery techniques.
"Both methods utilize a building block approach in the construction of molecules," says Fesik.
"However, in combinatorial chemistry, a very large number of molecules - ranging from the thousands
to the millions - are typically synthesized and tested for activity. In SAR by NMR, only a few
compounds, usually fewer than 10, need to be prepared. The chemistry is highly focused on linking
together molecules that have been experimentally demonstrated to bind to the protein target using
structural information on how they interact."
The Abbott team demonstrated the utility of the technique by the rapid discovery of compounds that
bind tightly to the receptor protein for the potent immunosuppressant, FK506. Using SAR by NMR, the
team completed what would ordinarily be a multi-year process in under six months.
"SAR by NMR can shorten the route to drug discovery by orders of magnitude," says Alan Rosenthal,
Ph.D., vice president, pharmaceuticaI discovery, at Abbott. "What we hope that means is that we'll be
able to develop more drugs, faster, to help the people who need them."
While Abbott has filed patent applications on the SAR by NMR method, the company pIans to make
the technology available to other drug developers.
"This is too important a tool to keep to ourselves," says Andre G. Pernet, Ph.D., Abbott's corporate
vice president, pharmaceutical research and development. "We believe this will become a dominant
technology in drug research, and making it available will help speed the creation of valuabIe new
medicines. SAR by NMR can improve the efforts of every lab involved in drug discovery." |
