thalidomide   Click here for help

GtoPdb Ligand ID: 7327

Synonyms: K-17
Approved drug Immunopharmacology Ligand
thalidomide is an approved drug (FDA (1998), EMA (2008))
Compound class: Synthetic organic
Comment: Thalidomide is principally an immunomodulatory drug. It inhibits synthesis of TNFα. Mechanistically, thalidomide binds to cereblon, and this complex recruits substrate proteins for degradation by the ubiquitin system. The lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) have been identified as substrates for thalidomide-bound cereblon. More recently another transcription factor, PLZF (ZBTB16), has been reported as a potential thalidomide/cereblon substrate [7]. Knockdown of Plfz induces skeletal abnormalities in chicken limbs, so thalidomide-targeted degradation of PLZF would be predicted to exhibit similar teratogenic effects.

SARS-CoV-2 and COVID-19: Thalidomide + low-dose glucocorticoid is being evaluated for efficacy in severe COVID-19 pneumonia (preprint available here An alternative approach is examining the combination of thalidomide + celecoxib (which targets NF-κB to suppress production of inflammatory cytokines; see preprint DOI: 10.13140/RG.2.2.26979.91689).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 87.04
Molecular weight 258.06
XLogP 0.92
No. Lipinski's rules broken 0
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Canonical SMILES OC1=NC(=O)C(CC1)N1C(=O)c2c(C1=O)cccc2
Isomeric SMILES OC1=NC(=O)C(CC1)N1C(=O)c2c(C1=O)cccc2
InChI InChI=1S/C13H10N2O4/c16-10-6-5-9(11(17)14-10)15-12(18)7-3-1-2-4-8(7)13(15)19/h1-4,9H,5-6H2,(H,14,16,17)
1. Eichner R, Heider M, Fernández-Sáiz V, van Bebber F, Garz AK, Lemeer S, Rudelius M, Targosz BS, Jacobs L, Knorn AM et al.. (2016)
Immunomodulatory drugs disrupt the cereblon-CD147-MCT1 axis to exert antitumor activity and teratogenicity.
Nat Med, 22 (7): 735-43. [PMID:27294876]
2. Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H. (2010)
Identification of a primary target of thalidomide teratogenicity.
Science, 327 (5971): 1345-50. [PMID:20223979]
3. Jo S, Lee KH, Song S, Jung YK, Park CS. (2005)
Identification and functional characterization of cereblon as a binding protein for large-conductance calcium-activated potassium channel in rat brain.
J Neurochem, 94 (5): 1212-24. [PMID:16045448]
4. Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M et al.. (2012)
Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide.
Leukemia, 26 (11): 2326-35. [PMID:22552008]
5. Mazzoccoli L, Cadoso SH, Amarante GW, de Souza MV, Domingues R, Machado MA, de Almeida MV, Teixeira HC. (2012)
Novel thalidomide analogues from diamines inhibit pro-inflammatory cytokine production and CD80 expression while enhancing IL-10.
Biomed Pharmacother, 66 (5): 323-9. [PMID:22770990]
6. Xin W, Xiaohua N, Peilin C, Xin C, Yaqiong S, Qihan W. (2008)
Primary function analysis of human mental retardation related gene CRBN.
Mol Biol Rep, 35 (2): 251-6. [PMID:17380424]
7. Yamanaka S, Murai H, Saito D, Abe G, Tokunaga E, Iwasaki T, Takahashi H, Takeda H, Suzuki T, Shibata N et al.. (2020)
PLZF is a new substrate of CRBN with thalidomide and 5-hydroxythalidomide.
bioRxiv, preprint. DOI: 10.1101/2020.02.28.969071