Word: aceing
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Dates: during 2000-2009
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...Tepper's team used this reasoning to try to improve on the popular blood-pressure-lowering drugs known as ACE inhibitors. These compounds inhibit an enzyme called angiotensin-converting enzyme (ACE), which is responsible for making the muscle cells in blood vessels contract, which drives blood pressure up. By interfering with the activity of this enzyme, ace inhibitors keep blood vessels relaxed and pressure down...
...ACE inhibitors currently on the market don't work on everyone, and Millennium figured that the genome might help them find a better version. So researchers sat down at their computers, plugged in some genetic sequences found in the gene for ACE and came up with 10,000 genes that might have comparable activity...
Then they used Zeus to set up microarray analyses and winnowed the 10,000 down to one promising protein they call ACE-2. Testing the enzyme on tissue cells from different organs in the body, the scientists showed that whereas the original ACE acts broadly on many tissues in the body, ACE-2 is particularly active in heart and kidney cells, where it might be more effective in controlling high blood pressure. Because they already knew on the molecular level exactly how ace worked, Tepper's team also knew precisely which lab tests would determine whether ACE...
...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...
...last step for the ACE-2 inhibitor, as for any drug, is human clinical trials. Because the Food and Drug Administration requires such rigorous testing, this is by far the most expensive part of drug development. So for human trials in some cases, Millennium has formed partnerships with large pharmaceutical companies that have the necessary resources and will share in any eventual profits...