Immunomodulatory imide drug

Immunomodulatory imide drug
Drug class
Thalidomide
Class identifiers
Use Erythema nodosum leprosum, multiple myeloma, myelodysplastic syndrome, acute myeloid leukaemia and other immunologic conditions
ATC code L04AX
Biological target TNF, IL-6, VEGF, NF-kB, etc.
Clinical data
Drugs.com Drug Classes
In Wikidata

Immunomodulatory imide drugs (IMiDs) are a class of immunomodulatory drugs[1] (drugs that adjust immune responses) containing an imide group. The IMiD class includes thalidomide and its analogues (lenalidomide, pomalidomide, and apremilast).[1]

The name "IMiD" alludes to both "IMD" for "immunomodulatory drug" and the forms imide, imido-, imid-, and imid.

Generations

There are three generations of IMiDs, with each successive generation being better tolerated and more active against inflammatory and malignant conditions.[1]

Medical use

The primary use of IMiDs in medicine is in the treatment of cancers and autoimmune diseases (including one that is a response to the infection leprosy).[2] Indications for these agents that have received regulatory approval include:[3]

Off-label indications for which they seem promising treatments include:[4]

Adverse effects

The major toxicities of approved IMiDs are peripheral neuropathy, thrombocytopenia, anaemia and venous thromboembolism.[4] There may be an increased risk of secondary malignancies, especially acute myeloid leukaemia in those receiving IMiDs.[4]

Mechanism of action

Their mechanism of action is not entirely clear, but it is known that they inhibit the production of tumour necrosis factor, interleukin 6 and immunoglobulin G and VEGF (which leads to its anti-angiogenic effects), co-stimulates T cells and NK cells and increases interferon gamma and interleukin 2 production.[5][6][7] Their teratogenic effects appear to be mediated by binding to cereblon.[8] Apremilast, on the other hand, inhibits PDE4.[4]

References

  1. 1 2 3 Knight, R (August 2005). "IMiDs: a novel class of immunomodulators". Seminars in Oncology. 32 (4 Suppl 5): S24–S30. doi:10.1053/j.seminoncol.2005.06.018. PMID 16085014.
  2. ↑ Pan, B; Lentzsch, S (October 2012). "The application and biology of immunomodulatory drugs (IMiDs) in cancer". Pharmacology & Therapeutics. 136 (1): 56–68. doi:10.1016/j.pharmthera.2012.07.004. PMID 22796518.
  3. ↑ Sedlarikova, L; Kubiczkova, L; Sevcikova, S; Hajek, R (October 2012). "Mechanism of immunomodulatory drugs in multiple myeloma". Leukemia Research. 36 (10): 1218–1224. doi:10.1016/j.leukres.2012.05.010. PMID 22727252.
  4. 1 2 3 4 Vallet, S; Witzens-Harig, M; Jaeger, D; Podar, K (March 2012). "Update on immunomodulatory drugs (IMiDs) in hematologic and solid malignancies". Expert Opinion on Pharmacotherapy. 13 (4): 473–494. doi:10.1517/14656566.2012.656091. PMID 22324734.
  5. ↑ Quach, H; Ritchie, D; Stewart, AK; Neeson, P; Harrison, S; Smyth, MJ; Prince, HM (January 2010). "Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma" (PDF). Leukemia. 24 (1): 22–32. doi:10.1038/leu.2009.236. PMC 3922408. PMID 19907437.
  6. ↑ Andhavarapu, S; Roy, V (February 2013). "Immunomodulatory drugs in multiple myeloma". Expert Review of Hematology. 6 (1): 69–82. doi:10.1586/ehm.12.62. PMID 23373782.
  7. ↑ Sedlarikova, L; Kubiczkova, L; Sevcikova, S; Hajek, R (October 2012). "Mechanism of immunomodulatory drugs in multiple myeloma". Leukemia Research. 36 (10): 1218–1224. doi:10.1016/j.leukres.2012.05.010. PMID 22727252.
  8. ↑ Chang, XB; Stewart, AK (2011). "What is the functional role of the thalidomide binding protein cereblon?" (PDF). International Journal of Biochemistry and Molecular Biology. 2 (3): 287–94. PMC 3193296. PMID 22003441.
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