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The evolution of thalidomide and its IMiD derivatives as anticancer agents

Nature Reviews Cancer volume 4, pages 314–322 (2004)Cite this article

Abstract

Thalidomide was originally used to treat morning sickness, but was banned in the 1960s for causing serious congenital birth defects. Remarkably, thalidomide was subsequently discovered to have anti-inflammatory and anti-angiogenic properties, and was identified as an effective treatment for multiple myeloma. A series of immunomodulatory drugs — created by chemical modification of thalidomide — have been developed to overcome the original devastating side effects. Their powerful anticancer properties mean that these drugs are now emerging from thalidomide's shadow as useful anticancer agents.

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Figure 1: Tumour-necrosis factor-α has numerous targets.
Figure 2: Co-stimulatory activity of thalidomide.
Figure 3: Structure of thalidomide and the IMiDs CC-5013 and CC-4047.
Figure 4: Antitumour activity of IMiDs in multiple myeloma.
Figure 5: The potential mechanisms of IMiD-mediated antitumour activity.

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Author information

Authors and Affiliations

  1. the Department of Cellular & Molecular Medicine, St George's Hospital Medical School, Cranmer Terrace, London, SW17 0RE, UK

    Keith Dredge & Angus G. Dalgleish

  2. Celgene Corporation, 7 Powder Horn Drive, Warren, 07059, New Jersey, USA

    J. Blake Bartlett

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  1. J. Blake Bartlett
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Correspondence to J. Blake Bartlett.

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Competing interests

J. Blake Bartlett is a group leader in Biology/Drug Discovery at Celgene Corporation. Angus G. Dalgleish is employed as a consultant for Celgene and holds stock in the company.

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DATABASES

Cancer.gov

colorectal cancer

glioma

melanoma

multiple myeloma

myelodysplastic syndromes

prostate cancer

renal cancer

LocusLink

CD28

IL-12

IL-6

TNF-α

TRAIL

vascular endothelial growth factor

OMIM

Behcet's disease

systemic lupus erythematosus

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Bartlett, J., Dredge, K. & Dalgleish, A. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer 4, 314–322 (2004). https://doi.org/10.1038/nrc1323

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