Immunomodulatory imide drugs (IMiDs)

Thalidomide and its relatives: «molecular glues» that make the cell's cereblon complex destroy proteins myeloma cells need. All are potent teratogens.

Updated Nov 1, 2026

What they are

Thalidomide, lenalidomide and pomalidomide, oral drugs built around the same glutarimide ring. They are central to the treatment of multiple myeloma; lenalidomide also treats myelodysplastic syndrome with deletion 5q and some lymphomas, and thalidomide treats erythema nodosum leprosum. Decades ago, given for morning sickness, thalidomide caused severe limb defects (phocomelia) in many children, so thalidomide and lenalidomide are dispensed only under strict pregnancy-prevention programmes.

Mechanism of action

IMiDs bind cereblon, the substrate receptor of a cullin-RING E3 ubiquitin ligase. Bound drug reshapes cereblon's surface so it grabs proteins it normally ignores, such as the transcription factors Ikaros and Aiolos (and CK1α for lenalidomide). These are tagged with ubiquitin and destroyed by the proteasome. Myeloma cells that depend on them die, T and natural killer cells become more active, and the drugs also have anti-angiogenic and anti-inflammatory effects.

Target: Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase

Drugs in this class

Others in the class

pomalidomide

Test yourself

Think of the answer, then tap the question to see it.

What protein do thalidomide and lenalidomide bind?

Cereblon, the substrate receptor of the CRL4 E3 ubiquitin ligase.

Why are IMiDs called «molecular glues»?

They stick a new set of proteins (Ikaros, Aiolos, CK1α) onto cereblon, which then tags them for destruction by the proteasome.

Which birth defect made thalidomide notorious?

Phocomelia: severely shortened or absent limbs.

Which serious vascular complication requires prevention in myeloma patients on IMiDs?

Deep vein thrombosis and pulmonary embolism (and arterial thrombosis), especially with dexamethasone.

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