Stories about: thalidomide

From thalidomide to Pomalyst: Better living through chemistry

Thalidomide advertisement, c. 1961
Thalidomide advertisement, c. 1961

In times past, a pharmaceutical chemist’s main focus was to synthesize novel molecules to treat diseases. Today, an increasingly popular alternative is to re-engineer an existing drug—and continually improve it even after FDA approval. That’s how Robert D’Amato, MD, PhD, developed Pomalyst®, recently approved to treat multiple myeloma and the most potent analog to date of thalidomide.

Pomalyst_CelgeneCorpThalidomide has its own fascinating history. Originally developed by Chemie Grünenthal GmbH in the 1950s, it was the result of a search for an anti-anxiety drug to compete with Valium, and was approved for use in Europe as a sleep aid and depression treatment. Eventually, doctors found it useful for treating nausea, and started prescribing it off-label to pregnant women with morning sickness.

The results were disastrous. Thalidomide turned out to be a teratogen, causing severe birth defects. 

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Predicting the probability of a tragedy: A model for teratogenicity

Congenital malformation of the feet caused by thalidomide.

The question comes up when a pregnant woman has a serious medical condition: should she or shouldn’t she be treated? Are the indicated drugs safe for the baby?

Drugs are assigned pregnancy risk classes. Thalidomide, whose reputation for causing fetal malformations was chillingly established in the 1960s, is solidly in Class X (the most risky), as are the cholesterol-lowering drug lovastatin and the anti-coagulant warfarin. At the other extreme are Class A drugs that are widely recognized as safe in pregnancy.

But between these extremes is a huge group of drugs for which little is known.

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