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)
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
cereblon Hs None Binding 8.1 pKd - 2
pKd 8.1 (Kd 8.5x10-9 M) [2]
Description: Determined in a BiaCore assay using immobilised thalidomide and recombinant cereblon protein.