1.0 2009-07-30 17:59:11 UTC 2026-05-14 16:56:32 UTC T3D3539 Thalidomide SmallMolecule Thalidomide belongs to the isoindolines, a subclass of isoindoles and derivatives within the organic compounds. This exogenous solid has the formula C13H10N2O4 and an average molecular weight of 258.23 g/mol. It functions as a drug (PMC10316824, PMC7186126), inhibitor (PMC13125077), and agonist (PMC5776038). Its recorded biological roles and applications include use as an immunosuppressive agent, anti-inflammatory agent (PMC10316824), anti-inflammatory drug, antineoplastic agent, angiogenesis inhibitor, leprostatic drug, teratogenic agent, sedative, antiemetic, and anticonvulsant. It is administered via the oral exposure route and is found in healthcare, pharmaceuticals, and veterinary products as an immunosuppressant, as well as in various electrical equipment, household cleaning and consumer products, and food processing sources. The compound targets several proteins, including Protein cereblon (CRBN), Tumor necrosis factor (TNF), Nuclear factor NF-kappa-B p105 subunit (NFKB1), Prostaglandin G/H synthase 2 (PTGS2), Hepatocyte nuclear factor 4-alpha (HNF4A), Nuclear receptor subfamily 1 group I member 2 (NR1I2), and is a binder of Fibroblast growth factor receptor 2 (FGFR2). In patients with erythema nodosum leprosum (ENL), its immunologic effects may relate to the down-modulation of selected cell surface adhesion molecules and the suppression of excessive tumor necrosis factor-alpha (TNF-a) production. Thalidomide is used as a treatment for cancer (PMC10216254, PMC4084783), multiple myeloma (PMC10216254, PMC10316824, PMC11158875, PMC11201495, PMC11637717, PMC12650601, PMC12923561, PMC13187128, PMC1779467, PMC2330021), angiosarcoma (PMC3715084, PMC5102718), rheumatoid arthritis (PMC1010320, PMC7298168), cutaneous lupus erythematosus (PMC9724583), pulmonary fibrosis (PMC9724583), gastrointestinal bleeding (PMC4986528, PMC6360670), pancytopenia (PMC4718299), vomiting (PMC8546762, PMC9903622), and bleeding (PMC12863811, PMC2776553, PMC5370822). It has therapeutic effects on inflammation (PMC6415974, PMC9724583), dilated cardiomyopathy (PMC4380242), pulmonary fibrosis (PMC5677010), rheumatoid arthritis (PMC4408009), gastrointestinal bleeding (PMC4250877), and multiple myeloma (PMC4084783, PMC4889030, PMC7298168). Associated health effects include neuropathy (PMC3674591, PMC4382664, PMC6081177, PMC7271593, PMC9387014, PMC9530276), drowsiness (PMC12863811, PMC9530276), fatigue (PMC3134146, PMC5370822, PMC6415974), rash (PMC3134146, PMC6212999), Stevens-Johnson syndrome (PMC3134146), neutropenia (PMC4439262, PMC5927128), edema (PMC4436674), increased headache (PMC5927128), and prostate cancer (PMC4439262). Drug Synthetic Toxin Organic Compound Amine Amide Ester Drug Leprostatic Agent Immunosuppressive Agent Metabolite Angiogenesis Inhibitor Teratogen Synthetic Compound Human Neurotoxin (+-)-N-(2,6-dioxo-3-Piperidyl)phthalimide (+-)-Thalidomide (±)-N-(2,6-dioxo-3-piperidyl)phthalimide (±)-thalidomide 1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)isoindoline 2,6-dioxo-3-phthalimidopiperidine 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione 3-Phthalimidoglutarimide Acid chlorides, C6-8-neo- alpha-(N-Phthalimido)glutarimide alpha-N-Phthalylglutaramide alpha-Phthalimidoglutarimide Contergan Distaval Fatty acids, C9-13-neo- Fatty acids, C9-13-neo-, cobalt salts K-17 N-(2,6-dioxo-3-piperidyl)phthalimide N-Phthalimidoglutamic acid imide N-Phthaloylglutamimide N-Phthalyl-glutaminsaeure-imid N-Phthalylglutamic acid imide Pro-ban M Sedalis Softenon Talidomida Talimol Thaled Thalidomidum Thalidomine USP26 Thalomid α-(N-phthalimido)glutarimide α-N-phthalylglutaramide α-phthalimidoglutarimide C13H10N2O4 258.2295 258.064056818 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione thalidomide 50-35-1 O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12 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) UEJJHQNACJXSKW-UHFFFAOYSA-N Organic compounds Organoheterocyclic compounds Isoindoles and derivatives Isoindolines Phthalimides Alpha amino acids and derivatives Azacyclic compounds Benzenoids Carbonyl compounds Delta lactams Dicarboximides Hydrocarbon derivatives Isoindoles N-substituted carboxylic acid imides N-unsubstituted carboxylic acid imides Organic oxides Organonitrogen compounds Organopnictogen compounds Piperidinediones Alpha-amino acid or derivatives Aromatic heteropolycyclic compound Azacycle Benzenoid Carbonyl group Carboxylic acid derivative Carboxylic acid imide Carboxylic acid imide, n-substituted Carboxylic acid imide, n-unsubstituted Delta-lactam Dicarboximide Hydrocarbon derivative Isoindole Lactam Organic nitrogen compound Organic oxide Organic oxygen compound Organonitrogen compound Organooxygen compound Organopnictogen compound Phthalimide Piperidine Piperidinedione Piperidinone Aromatic heteropolycyclic compounds phthalimides piperidones Detected and Not Quantified Exogenous Cytoplasm Extracellular Membrane Thalidomide Drug Metabolism Action Pathway SMP0143467 Thalidomide Predicted Metabolism Pathway SMP0174846 Solid Thalidomide is an off-white to white, odorless, crystalline powder. melting_point 270°C solubility 545 mg/L (at 25°C) logp 0.33 logp 0.42 ALOGPS logs -2.00 ALOGPS solubility 2.55e+00 g/l ALOGPS logp 0.016 ChemAxon pka_strongest_acidic 11.59 ChemAxon pka_strongest_basic -6.4 ChemAxon iupac 2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione ChemAxon average_mass 258.2295 ChemAxon mono_mass 258.064056818 ChemAxon smiles O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12 ChemAxon formula C13H10N2O4 ChemAxon 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) ChemAxon inchikey UEJJHQNACJXSKW-UHFFFAOYSA-N ChemAxon polar_surface_area 83.55 ChemAxon refractivity 64.32 ChemAxon polarizability 24.42 ChemAxon rotatable_bond_count 1 ChemAxon acceptor_count 4 ChemAxon donor_count 1 ChemAxon physiological_charge 0 ChemAxon formal_charge 0 ChemAxon The 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&rsquo;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. In 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. The 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. At 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&#8482; (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. The 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. No indication of carcinogenicity to humans (not listed by IARC). For 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. #<HealthEffect::ActiveRecord_Associations_CollectionProxy:0x00007f3bae3ba470> Thalidomide is associated with drowsiness/somnolence, peripheral neuropathy, dizziness/orthostatic hypotension, neutro-penia, and HIV viral load increase. Precipitation 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. (L1721) DB01041 HMDB15175 5426 CHEMBL468 5233 C07910 9513 Thalidomide Thalidomide 18048412 RxList: The Internet Drug Index (2009).: http://www.rxlist.com/thalomid-drug.htm BE0000262 In 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. IC50 0.5 uM BindingDB 50070114 BE0000704 In 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. BE0004796 BE0001086 In 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. BE0000748 BE0004898 BE0004755 BE0004879 BE0004019 AC50 4.19 uM ATG_HNF4a_TRANS Attagene BE0000956 AC50 5.58 uM ATG_PXR_TRANS Attagene BE0000925 BE0003663