thalidomide

Thalidomide is a synthetic imide drug with immunomodulatory, antiangiogenic, and anti-inflammatory properties. It was originally developed in 1957 by the German company Grünenthal as a sedative and antiemetic for pregnant women and was marketed in many countries as a remedy for morning sickness. It was widely prescribed and initially regarded as safe for use during pregnancy.

In the early 1960s, thalidomide was linked to a wave of birth defects, most notably limb malformations such as phocomelia, along with deafness, heart and eye abnormalities, and other congenital problems. It is estimated that tens of thousands of babies in dozens of countries were affected, with about 10,000–12,000 severely disabled births attributed to the drug before its withdrawal from markets. The connection was first noted by doctors such as William McBride in Australia and led to heightened regulatory scrutiny worldwide. In the United States, FDA reviewer Frances Oldham Kelsey refused to approve the drug in 1960, contributing to later regulatory reforms; Kefauver–Harris amendments in 1962 strengthened drug testing and safety requirements.

Thalidomide was reintroduced in the United States in 1998 under strict controls and is now used to treat certain conditions, including erythema nodosum leprosum and multiple myeloma, often in combination with other agents. Its use is tightly regulated under REMS programs due to its teratogenic risk. Mechanistically, thalidomide acts as an immunomodulatory drug that can affect cereblon and downstream transcription factors, contributing to its clinical effects and its well-known safety concerns.