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# 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

## Key points

- Teratogens: thalidomide causes phocomelia (stunted limbs); lenalidomide is handled the same way. Pregnancy tests, effective contraception and restricted dispensing programmes are mandatory, and men use condoms because the drug reaches semen.
- Venous and arterial thromboembolism, especially with dexamethasone or other chemotherapy in myeloma: thromboprophylaxis is usual.
- Thalidomide: sedation, constipation and dose-limiting peripheral neuropathy. Lenalidomide: neutropenia and thrombocytopenia instead.
- Mechanism in one line: a «molecular glue» that makes cereblon mark Ikaros and Aiolos for proteasomal destruction.

## Drugs in this class

- [**Lenalidomide** Oral thalidomide derivative that makes cereblon destroy Ikaros and Aiolos. A myeloma mainstay; teratogenic, so it is… Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase](https://durgical.com/en/pharmacology/lenalidomide/)
- [**Thalidomide** The sedative that caused the phocomelia disaster, now used for multiple myeloma and leprosy reactions under strict… Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase](https://durgical.com/en/pharmacology/thalidomide/)
- [**Pomalidomide** A thalidomide relative for relapsed multiple myeloma and Kaposi sarcoma. Strong birth-defect risk, clots and low blood… Cereblon (CRBN), substrate receptor of the CRL4 E3 ubiquitin ligase](https://durgical.com/en/pharmacology/pomalidomide/)

## 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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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [DailyMed - LENALIDOMIDE capsule](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9943e098-20b0-dbb3-af12-7816eedd3f70) (DailyMed (U.S. National Library of Medicine), 2026); [Thalidomide: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a699032.html) (MedlinePlus (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/immunomodulatory-imide-drugs/