Thalidomide (CHEM002534)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (10)XML
Record Information
Version1.0
Creation Date2009-07-30 17:59:11 UTC
Update Date2026-03-31 17:50:14 UTC
Accession NumberCHEM002534
Identification
Common NameThalidomide
ClassSmall Molecule
DescriptionA piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor-alpha from monocytes, and modulates other cytokine action. [PubChem]
Contaminant Sources
  • HMDB Contaminants - Urine
  • HPV EPA Chemicals
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Amide
  • Amine
  • Angiogenesis Inhibitor
  • Drug
  • Ester
  • Immunosuppressive Agent
  • Leprostatic Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Teratogen
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
ThalomidKegg
ThaledKegg
alpha-PhthalimidoglutarimideHMDB
N-Phthalimidoglutamic acid imideHMDB
N-PhthaloylglutamimideHMDB
N-Phthalylglutamic acid imideHMDB
Thalidomine usp26HMDB
SedovalHMDB
Celgene brand OF thalidomideHMDB
ThalidomideMeSH
Chemical FormulaC13H10N2O4
Average Molecular Mass258.230 g/mol
Monoisotopic Mass258.064 g/mol
CAS Registry Number50-35-1
IUPAC Name2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
Traditional Namethalidomide
SMILESO=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12
InChI IdentifierInChI=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)
InChI KeyUEJJHQNACJXSKW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phthalimides. These are aromatic heterocyclic compounds containing a 1,3-dioxoisoindoline moiety. They are imide derivatives of phthalic anhydrides.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIsoindoles and derivatives
Sub ClassIsoindolines
Direct ParentPhthalimides
Alternative Parents
Substituents
  • Phthalimide
  • Alpha-amino acid or derivatives
  • Isoindole
  • Piperidinedione
  • Delta-lactam
  • Piperidinone
  • Benzenoid
  • Piperidine
  • Carboxylic acid imide, n-substituted
  • Carboxylic acid imide
  • Dicarboximide
  • Carboxylic acid imide, n-unsubstituted
  • Lactam
  • Carboxylic acid derivative
  • Azacycle
  • Organic nitrogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceThalidomide is an off-white to white, odorless, crystalline powder.
Experimental Properties
PropertyValue
Melting Point270°C
Boiling PointNot Available
Solubility545 mg/L (at 25°C)
Predicted Properties
PropertyValueSource
Water Solubility2.55 g/LALOGPS
logP0.42ALOGPS
logP0.016ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)11.59ChemAxon
pKa (Strongest Basic)-6.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area83.55 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity64.32 m³·mol⁻¹ChemAxon
Polarizability24.42 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05d0-4950000000-f29254c7cc48a749c100Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-1940000000-f6d6997d1eaa7a83ec1bSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0930000000-e92e8e23d5db87f50f53Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0019-2900000000-ecfd1b7ec17b857ea977Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0930000000-e92e8e23d5db87f50f53Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-1940000000-f6d6997d1eaa7a83ec1bSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-2900000000-ecfd1b7ec17b857ea977Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0aou-3910000000-91636cf8948ff2a1ec8cSpectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0aou-4900000000-0354536dffa9acdee12dSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-066u-6900000000-ea3e7b4b381e65a7c9a4Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-0aou-4900000000-c5062441ebfb6523331bSpectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-0bvl-2970000000-1e251d07e623c9fbe2a2Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0aou-3910000000-19940b0b041ba51e96e0Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-0a6r-0190000000-a818a5ae6100d0f996baSpectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-0a4i-0090000000-42e8be928c8508c213f2Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0bvl-2970000000-fcf57e68d7f7156f09d4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0090000000-094c39302b7589d69293Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-0590000000-a8eb9abb005e68bb1fdfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000f-9800000000-e219527727ba0e4f62ddSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0190000000-88a6f8cb2bfe0f1b603fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bti-1790000000-bdf020cb11e65e0077f7Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01oy-9700000000-ce19845489ffe3fdb389Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0bta-0960000000-38a7ecf36472375bfe14Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4j-1590000000-40230dba1a083dee9f10Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0005-4900000000-b49c37804603e0525f05Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052b-0960000000-d36ac6ec3b1b89dff27dSpectrum
MSMass Spectrum (Electron Ionization)splash10-0wba-4900000000-77362eaf27267f59650dSpectrum
Toxicity Profile
Route of ExposureThe absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. In studies of both healthy volunteers and subjects with Hansen’s disease, the mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours indicating that thalidomide is slowly absorbed from the gastrointestinal tract.
Mechanism of ToxicityIn patients with erythema nodosum leprosum (ENL) the mechanism of action is not fully understood. Available data from in vitro studies and preliminary clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-a) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-a in patients with ENL, however, it has also been shown to increase plasma TNF-a levels in HIV-seropositive patients. As a cancer treatment, the drug may act as a VEGF inhibitor.
MetabolismAt the present time, the exact metabolic route and fate of thalidomide is not known in humans. Thalidomide itself does not appear to be hepatically metabolized to any large extent, but appears to undergo non-enzymatic hydrolysis in plasma to multiple metabolites. Thalidomide may be metabolized hepatically by enzymes of the cytochrome P450 enzyme system. The end product of metabolism, phthalic acid, is excreted as a glycine conjugate. In a repeat dose study in which THALOMID™ (thalidomide) 200 mg was administered to 10 healthy females for 18 days, thalidomide displayed similar pharmacokinetic profiles on the first and last day of dosing. This suggests that thalidomide does not induce or inhibit its own metabolism. Route of Elimination: Thalidomide itself has less than 0.7% of the dose excreted in the urine as unchanged drug. Half Life: The mean half-life of elimination ranges from approximately 5 to 7 hours following a single dose and is not altered upon multiple dosing.
Toxicity ValuesThe R-configuration and the S-configuration are more toxic individually than the racemic mixture. The LD50 could not be established in mice for racemic thalidomide, whereas LD50 values for the R and S configurations are reported to be 0.4 to 0.7 g/kg and 0.5 to 1.5 g/kg, respectively.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the acute treatment of the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). Also for use as maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL recurrence. Used to treat multiple myeloma.
Minimum Risk LevelNot Available
Health EffectsThe most serious toxicity associated with thalidomide is its documented human teratogenicity. The risk of severe birth defects, primarily phocomelia or death to the fetus, is extremely high during the critical period of pregnancy. The critical period is estimated, depending on the source of information, to range from 35 to 50 days after the last menstrual period. The risk of other potentially severe birth defects outside this critical period is unknown, but may be significant. Based on present knowledge, thalidomide must not be used at any time during pregnancy. Thalidomide can cause severe birth defects in humans.
SymptomsThalidomide is associated with drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutro-penia, and HIV viral load increase.
TreatmentPrecipitation of acyclovir in renal tubules may occur when the solubility (2.5 mg/mL) is exceeded in the intratubular fluid. In the event of acute renal failure and anuria, the patient may benefit from hemodialysis until renal function is restored. (2)
Concentrations
Not Available
DrugBank IDDB01041
HMDB IDHMDB0015175
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkThalidomide
Chemspider ID5233
ChEBI ID74947
PubChem Compound ID5426
Kegg Compound IDC07910
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

Jamshed Shah, “Synthesis and anti-tumor activity of nitrogen substituted thalidomide analogs.” U.S. Patent US20030139451, issued July 24, 2003.

MSDSLink
General ReferencesNot Available