Word: compounded
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Currently, Guilford Pharmaceuticals in Baltimore, Md., and Amgen in Thousand Oaks, Calif., are collaborating on a synthetic neurotrophic compound that can be taken orally and then travels to the brain, where it bonds with proteins in dopamine neurons. The tricky part is that most trophic molecules are too big to move across the miniscule blood vessels in the brain, so Guilford and Amgen are working on a smaller one that can get where it needs to go. The progress so far is promising. "We're in Phase 2 human trials now," says Dr. Craig Smith, president of Guilford. "Although...
...they moved quickly to develop a compound that inhibits ACE-2. Scientists combed through Millennium's library of 700 different classes of compounds for molecules whose chemistry made them candidates to clamp down on ACE-2 activity. Then, with the help of protein-modeling software (see Bioinformatics box), they manipulated the chemical structure of their new inhibitor to give it optimal binding affinity with the ACE-2 receptor. In about two years, Millennium had created a new blood-pressure-drug candidate that is now being tested in animals...
...will be carefully documented. Eventually the clinical data will be combined with the genetic studies. Says Herskowitz: "It's interesting to see the changes to the cell, but what you really want to know is how someone with that change would respond differently to Prozac, or to an anticancer compound. That's more elaborate, which is why this clinical aspect is exciting stuff...
ALZHEIMER'S DISEASE Scientists began safety testing the first drug designed to tackle the root cause rather than the symptoms of this brain-addling disease. Patients in the early stages of Alzheimer's were given a gamma secretase inhibitor, a compound that blocks the formation of the sticky plaques that gum up the brain's neural connections. So far, the drug seems to have been well tolerated...
Nature is not the only lode that drug developers are mining. Linezolid, the novel antibiotic just approved by the FDA, is totally synthetic, and that is a great advantage, believes Pharmacia Corp.'s Dr. Gary Tarpley, who led the team effort that produced the drug. "Because this compound has never been seen by bacteria," he says, "it is extremely unlikely that there is any pre-existing resistance out there." Like tetracycline, linezolid blocks protein synthesis, but it does so much earlier in the cellular cycle. No other antibiotic operates in this fashion, yet another reason to expect resistance to develop...