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COX activity is seen in common nonsteroidal
anti-inflammatory drugs like aspirin and ibuprofen. However, prolonged
use of COX inhibitors can result in a variety of negative side effects,
such as possible digestive and liver problems. Some COX inhibitors
have recently been pulled from the market due to an increased risk of
heart complications.
The protein transythyretin acts as a shuttle to
transport thyroxine, a hormone, throughout the body. As the least
important of the three blood proteins that carry thyroxine,
transthyretin also has a tendency to fall apart and form tough,
insoluble plaques, sometimes causing injury to delicate tissues.
Certain people are genetically more likely to have the proteins fall
apart, increasing the risks. Investigators have found that in
laboratory experiments, certain COX inhibitors help stabilize the
structure of transthyretin protein, and therefore prevent harmful
plaque formation.
"The successful identification of
carborane-containing surrogates for known COX inhibitors based
exclusively on carbon chemistry greatly strengthens the concept that
carboranes can be substituted for carbon-rich portions of known
pharmaceuticals, and in so doing, improve its efficacy and safety,"
said M. Frederick Hawthorne, professor of radiology and chemistry and
director of the International Institute for Nano and Molecular
Medicine.
Hawthorne and his fellow researchers have found
that carboranes can be useful in staving off the negative side effects
of COX inhibitors while still completing the task of preventing
protein plaque buildup. Carboranes are man-made small molecules that
are very stable. Because they are unnatural, the body does not
recognize carboranes. This lack of recognition has the benefit of
increasing drug circulation time as well as preventing the body from
metabolizing the drug into potentially damaging products. Due to their
unique structure, even direct carborane analogues of COX inhibitors
won't act as pain relievers but will do the beneficial work of
preventing protein plaque formation.
Next, researchers will test the carborane analogs
with the genetic variant proteins, hoping to find the new drugs to be
broadly applicable. Eventually, simple cellular tests will be
performed to look for toxicity, which will then lead to the
development of a simple animal model.
The technique of using carboranes and other boranes
in drug development also holds promise for treating other illnesses.
Like designing a set of keys that each fit only one lock, researchers
hope to use carboranes to make many other drugs that are very specific
and therefore reduce detrimental side effects.
"One day carboranes may become ubiquitous in the
pharmaceutical industry, they are ideal candidates for further
research," said Richard L. Julius, researcher at MU. |
