This news item was created by students Christian Dornhoefer, Mark Eilers, Ellen McDermott, Evan Thames and Brad Morgan as part of their Chemistry 210 Semester Project in WS99 under the guidance of Prof. Rainer Glaser.

Glaser's "Chemistry is in the News"
To Accompany Wade Organic Chemistry 4/e.
Chapter 24: Amino Acids, Peptides, and Proteins.

For each of the following questions, please refer to the following article:

'Fast Track' Drug to Treat Diabetes Tied to 33 Deaths
by David Willman, Los Angeles Times, December 6, 1998.

Editorial Comments

Type 2 diabetes, or adult onset diabetes, affects 15 million Americans, and is the seventh leading cause of death in the United States. High blood-sugar levels that can increase the risk of heart disease and cause other complications characterize type 2 diabetes. Currently, there are many drugs on the market that treat this disease. One such drug is Rezulin, a.k.a. Troglitazone.

Rezulin was developed by ( Warner-Lambert Co. and approved by the Food and Drug Administration (FDA) to be used in the treatment of Type 2 diabetes. Its intent was to lower blood-sugar levels by improving cell response to insulin.

Rezulin met its intention of lowering blood-sugar levels, but it turned out to have some serious side effects, the most serious being liver damage. It has been found that some patients taking Rezulin have developed sudden, idiosyncratic liver failure. Since its approval by the FDA in 1997, it has been linked to at least 33 deaths due to liver damage.

The drug took only six months to approve, which amounted to less than half the time the FDA normally takes to test new drugs. This is a result of new legislation put through by an alliance of Republicans, Democrats, and pharmaceutical industry lobbyists to force the FDA to approve drugs faster. As a result, drugs are being approved despite concerns that they have not been tested thoroughly.

This was the case with Rezulin. It was approved even though experiments showed that it might be toxic to the liver. The National Institutes of Health conducted a study in which one person died of liver failure while taking the drug. Despite this finding, the FDA was pressured into approving the drug, which they eventually did.

The FDA and Warner-Lambert now recommend that patients taking Rezulin undergo regular liver testing, hoping to detect any problems before they become life threatening. They contend that the drug is safe when used with liver-function monitoring.

Pertinent Text References
Chapter 24: Amino Acids, Peptides, and Proteins


Question 1: What is the molecular formula and IUPAC name given to Rezulin? (refer to Rezulin link from article)

A. molecular formula is C24H27NO5S, and the IUPAC name is (+/-5-[[4-[3,4-dihydro-6-hydroxy-2,5,7,8-tetramethyl- 2H-1-benzopyran-2-y1-methoxy]phenyl]methyl]-2,4-thiazolidinedione).

Question 2: What is the purpose of Rezulin, in other words, what does it do?

A. Rezulin resensitizes the body to insulin. In other words, it stimulates a gene to produce more insulin-controlled proteins that remove the sugar from the bloodstream.

Question 3: Why is Rezulin under investigation after it has already been approved?

A. It is under investigation because it has been linked to 33 deaths due to toxicity to the liver. Some patients taking Rezulin have developed sudden liver failure. In those cases, the liver swells and ceases to function.

Question 4: Chapter 24 talks about the structure of proteins. Insulin is a protein that controls blood-sugar levels. What is the molecular formula for insulin? How many peptide chains make up this protein? How are these chains held together?

A. The molecular formula for insulin is C257H387N65O66S6. Insulin is composed of 2 peptide chains. The a chain is composed of 21 amino acids, and the b chain is composed of 30 amino acids. The 2 chains are held together by disulfide bridges (S-S bonds).

Question 5: Republicans, Democrats, and pharmaceutical lobbyists have pressed for legislation to force the FDA to approve drugs quicker. Their reasoning was that people who have such disease as AIDS, cancer, diabetes, etc., are dying due to the long process the FDA takes in approving drugs. Do you think that they are right in trying to force the FDA to approve drugs faster for these patients, or do you think that the FDA should take the time it needs to ensure the drug is safe for the people taking them?