Discovery and development of thalidomide and its analogs

Thalidomide
Drug class
Thalidomide, the parent drug of thalidomide analogs.
Class identifiers
ATC code	L04AX
Biological target	Immunosuppressant

The development of analogs of thalidomide was precipitated by the discovery of the anti-angiogenic and anti-inflammatory properties of the drug yielding a new way of fighting cancer as well as some inflammatory diseases after it had been banned in 1961. The problems with thalidomide included; teratogenic side effects, high incidence of other adverse reactions, poor solubility in water and poor absorption from the intestines.

In 1998 thalidomide was approved by the U.S. Food and Drug Administration (FDA) for use in newly diagnosed multiple myeloma (MM) under strict regulations. This has led to the development of a number of analogs with fewer side effects and increased potency which include lenalidomide, pomalidomide and apremilast, all of which are currently marketed and manufactured by Celgene.

Thalidomide was originally released in the Federal Republic of Germany (West Germany) under the label of Contergan on October 1, 1957 by Chemie Grünenthal (now Grünenthal). The drug was primarily prescribed as a sedative or hypnotic, but it was also used as an antiemetic and sedative. The drug was banned in 1961 after its teratogenic properties were observed. The problems with thalidomide were, aside from the teratogenic side effects, both high incidence of other adverse reactions along with poor solubility in water and absorption from the intestines. Adverse reactions include peripheral neuropathy in large majority of patients, constipation, thromboembolism along with dermatological complications.