Thalidomide

Identification

Summary

Thalidomide is a medication used to treat cancers, particularly newly diagnosed multiple myeloma, and erythema nodosum leprosum.

Brand Names
Thalomid
Generic Name
Thalidomide
DrugBank Accession Number
DB01041
Background

A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, thalidomide was withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of inflammatory disorders and cancers. Thalidomide displays immunosuppressive and anti-angiogenic activity through modulating the release of inflammatory mediators like tumor necrosis factor-alpha (TNF-a) and other cytokine action. Due to severe teratogenicity, pregnancy must be excluded before the start of treatment and patients must enrol in the THALIDOMID Risk Evaluation and Mitigation Strategy (REMS) program to ensure contraception adherence.10

Type
Small Molecule
Groups
Approved, Investigational, Withdrawn
Structure
Weight
Average: 258.2295
Monoisotopic: 258.064056818
Chemical Formula
C13H10N2O4
Synonyms
  • (+-)-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
  • 3-Phthalimidoglutarimide
  • alpha-(N-Phthalimido)glutarimide
  • alpha-N-Phthalylglutaramide
  • N-(2,6-dioxo-3-piperidyl)phthalimide
  • N-Phthaloylglutamimide
  • N-Phthalyl-glutaminsaeure-imid
  • N-Phthalylglutamic acid imide
  • Talidomida
  • Thalidomide
  • Thalidomidum
  • α-(N-phthalimido)glutarimide
  • α-N-phthalylglutaramide
  • α-phthalimidoglutarimide
External IDs
  • NSC-527179
  • NSC-66847

Pharmacology

Indication

Thalidomide is primarily used for the acute treatment and maintenance therapy to prevent and suppress the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL).10

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAphthous stomatitis••• ••••••••••••
Treatment ofChronic graft-versus-host disease••• ••••••••••••
Prevention ofErythema nodosum leprosum•••••••••••••••••••
Used in combination to manageLight-chain amyloidosisRegimen in combination with: Dexamethasone (DB01234), Cyclophosphamide (DB00531)••• ••••••••••••
Used in combination to treatMultiple myelomaRegimen in combination with: Dexamethasone (DB01234)•••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Thalidomide, originally developed as a sedative, is an immunomodulatory and anti-inflammatory agent with a spectrum of activity that is not fully characterized. However, thalidomide is believed to exert its effect through inhibiting and modulating the level of various inflammatory mediators, particularly tumor necrosis factor-alpha (TNF-a) and IL-6. 5 Additionally, thalidomide is also shown to inhibit basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), suggesting a potential anti-angiogenic application of thalidomide in cancer patients. 6

Thalidomide is racemic — it contains both left and right handed isomers in equal amounts: the (+)R enantiomer is effective against morning sickness, and the (−)S enantiomer is teratogenic. The enantiomers are interconverted to each other in vivo; hence, administering only one enantiomer will not prevent the teratogenic effect in humans 7.

Mechanism of action

The mechanism of action of thalidomide is not fully understood. Previous research indicate that thalidomide binds to cerebron, a component of the E3 ubiquitin ligase complex, to selectively degrade the transcription factor IKZF3 and IKZF1. These 2 transcription factors are vital for the proliferation and survival of malignant myeloma cells. 2

Regarding TNF-alpha, thalidomide seems to block this mediator via a variety of mechanism. Thalidomide can inhibit the expression myeloid differentiating factor 88 (MyD88), an adaptor protein that is involved in the TNF-alpha production signalling pathway, at the protein and RNA level. Additionally, thalidomide prevents the activation of Nuclear Factor Kappa B (NF-kB), another upstream effector of the TNF-alpha production pathway. Finally, some evidences suggest that thalidomide can block alpha-1 acid glycoprotein (AGP), a known inducer of the NF-kB/MyD88 pathway, thus inhibiting the expression of TNF-alpha 8. The down-regulation of NF-kB and MyD88 can also affect the cross talk between the NF-kB/MyD88 and VEGF pathway, resulting in thalidomide's anti-angiogenic effect. 9

TargetActionsOrganism
AProtein cereblon
inhibitor
Humans
ADNA
intercalation
Humans
Aalpha1-acid glycoprotein
binder
Humans
Absorption

The absolute bioavailability has not yet been characterized in human subjects due to its poor aqueous solubility. The mean time to peak plasma concentrations (Tmax) ranged from 2.9 to 5.7 hours following a single dose from 50 to 400 mg. Patients with Hansen’s disease may have an increased bioavailability of thalidomide, although the clinical significance of this is unknown. 10

Due to its low aqueous solubility and thus low dissolution is the gastrointestinal tract, thalidomide's absorption is slow, with a tlag of 20-40 min. Therefore, thalidomide exhibits absorption rate-limited pharmacokinetics or "flip-flop" phenomenon. Following a single dose of 200 mg in healthy male subjects, cmax and AUC were calculated to be 2.00 ± 0.55 mg/L and 19.80 ± 3.61 mg*h/mL respectively. 4

Volume of distribution

The volume of distribution of thalidomide is difficult to determine due to spontaneous hydrolysis and chiral inversion, but it is estimated to be 70-120 L. 4,1

Protein binding

The mean plasma protein binding is 55% and 66% for the (+)R and (−)S enantiomers, respectively. 10

Metabolism

Thalidomide appears to undergo primarily non-enzymatic hydrolysis in plasma to multiple metabolites, as the four amide bonds in thalidomide allow for rapid hydrolysis under physiological pH. 3

Evidences for enzymatic metabolism of thalidomide is mixed, as in vitro studies using rat liver microsome have detected 5-hydroxythalidomide (5-OH), a monohydroxylated metabolite of thalidomide catalyzed by the CYP2C19 enzyme, and the addition of omeprazole, a CYP2C19 inhibitor, inhibits the metabolism of thalidomide. 3 5-hydroxythalidomide (5-OH) has also been detected in the plasma of 32% of androgen-independent prostate cancer patients undergoing oral thalidomide treatment.3 However, significant interspecies difference in thalidomide metabolism has been noted, potentially signifying that animals like rats and rabbits rely on enzymatic metabolism of thalidomide more than human.3

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Route of elimination

Thalidomide is primarily excreted in urine as hydrolytic metabolites since less than 1% of the parent form is detected in the urine. Fecal excretion of thalidomide is minimal. 10

Half-life

The half-life of thalidomide in healthy male subjects after a single dose of 200 mg is 6.17 ± 2.56 h. 3

Clearance

The oral clearance of thalidomide is 10.50 ± 2.10 L/h. 3

Adverse Effects
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Toxicity

The oral LD50 in rats is 113 mg/kg and 2 g/kg in mouse.11

Two-year carcinogenicity studies were conducted in male and female rats and mice. No compound-related tumorigenic effects were observed at the highest dose levels of 3,000 mg/kg/day to male and female mice (38-fold greater than the highest recommended daily human dose of 400 mg based upon body surface area [BSA]), 3,000 mg/kg/day to female rats (75-fold the maximum human dose based upon BSA), and 300 mg/kg/day to male rats (7.5-fold the maximum human dose based upon BSA). 10

Thalidomide was neither mutagenic nor genotoxic in the following assays: the Ames bacterial (S. typhimurium and E. coli) reverse mutation assay, a Chinese hamster ovary cell (AS52/XPRT) forward mutation assay, and an in vivo mouse micronucleus test. 10

Fertility studies were conducted in male and female rabbits; no compound-related effects in mating and fertility indices were observed at any oral thalidomide dose level including the highest of 100 mg/kg/day to female rabbits and 500 mg/kg/day to male rabbits (approximately 5- and 25- fold the maximum human dose, respectively, based upon BSA). Testicular pathological and histopathological effects (classified as slight) were seen in male rabbits at dose levels ≥30 mg/kg/day (approximately 1.5-fold the maximum human dose based upon BSA). 10

There is no specific antidote for a thalidomide overdose. In the event of an overdose, the patient’s vital signs should be monitored and appropriate supportive care given to maintain blood pressure and respiratory status. 10

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-Benzodiazepine1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
AbaloparatideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Abaloparatide.
AbametapirThe serum concentration of Thalidomide can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Thalidomide can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Thalidomide.
Food Interactions
  • Avoid alcohol. Ingesting alcohol may increase the drowsiness caused by thalidomide.
  • Take after a meal. Wait at least 1 hour after eating before taking thalidomide.

Products

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International/Other Brands
Contergan / Distaval / K-17 / Pro-ban M / Sedalis / Softenon / Talimol / Thaled
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Thalidomide CelgeneCapsule50 mgOralBristol Myers Squibb Pharma Eeig2016-09-08Not applicableEU flag
Thalidomide LipomedTablet, coated100 mgOralLipomed2022-12-02Not applicableEU flag
ThalomidCapsule100 mg/1OralCelgene Corporation2003-06-20Not applicableUS flag
ThalomidCapsule150 mgOralCelgeneNot applicableNot applicableCanada flag
ThalomidCapsule200 mg/1OralCelgene Corporation2003-06-20Not applicableUS flag

Categories

ATC Codes
L04AX02 — Thalidomide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoindoles and derivatives
Sub Class
Isoindolines
Direct Parent
Phthalimides
Alternative Parents
Alpha amino acids and derivatives / Isoindoles / Piperidinediones / Delta lactams / N-substituted carboxylic acid imides / Benzenoids / N-unsubstituted carboxylic acid imides / Dicarboximides / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
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
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidones, phthalimides (CHEBI:74947)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
4Z8R6ORS6L
CAS number
50-35-1
InChI Key
UEJJHQNACJXSKW-UHFFFAOYSA-N
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)
IUPAC Name
2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
SMILES
O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC=C12

References

Synthesis Reference

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

US20030139451
General References
  1. Eriksson T, Bjorkman S, Hoglund P: Clinical pharmacology of thalidomide. Eur J Clin Pharmacol. 2001 Aug;57(5):365-76. doi: 10.1007/s002280100320. [Article]
  2. Kronke J, Udeshi ND, Narla A, Grauman P, Hurst SN, McConkey M, Svinkina T, Heckl D, Comer E, Li X, Ciarlo C, Hartman E, Munshi N, Schenone M, Schreiber SL, Carr SA, Ebert BL: Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science. 2014 Jan 17;343(6168):301-5. doi: 10.1126/science.1244851. Epub 2013 Nov 29. [Article]
  3. Lepper ER, Smith NF, Cox MC, Scripture CD, Figg WD: Thalidomide metabolism and hydrolysis: mechanisms and implications. Curr Drug Metab. 2006 Aug;7(6):677-85. doi: 10.2174/138920006778017777. [Article]
  4. Teo SK, Colburn WA, Tracewell WG, Kook KA, Stirling DI, Jaworsky MS, Scheffler MA, Thomas SD, Laskin OL: Clinical pharmacokinetics of thalidomide. Clin Pharmacokinet. 2004;43(5):311-27. doi: 10.2165/00003088-200443050-00004. [Article]
  5. Anderson KC: Lenalidomide and thalidomide: mechanisms of action--similarities and differences. Semin Hematol. 2005 Oct;42(4 Suppl 4):S3-8. [Article]
  6. Baidas S, Tfayli A, Bhargava P: Thalidomide: an old drug with new clinical applications. Cancer Invest. 2002;20(5-6):835-48. doi: 10.1081/cnv-120002498. [Article]
  7. Tokunaga E, Yamamoto T, Ito E, Shibata N: Understanding the Thalidomide Chirality in Biological Processes by the Self-disproportionation of Enantiomers. Sci Rep. 2018 Nov 20;8(1):17131. doi: 10.1038/s41598-018-35457-6. [Article]
  8. Majumder S, Sreedhara SR, Banerjee S, Chatterjee S: TNF alpha signaling beholds thalidomide saga: a review of mechanistic role of TNF-alpha signaling under thalidomide. Curr Top Med Chem. 2012;12(13):1456-67. doi: 10.2174/156802612801784443. [Article]
  9. Sherbet GV: Therapeutic Potential of Thalidomide and Its Analogues in the Treatment of Cancer. Anticancer Res. 2015 Nov;35(11):5767-72. [Article]
  10. FDA Approved Drug Products: Thalidomid (thalidomide) capsules for oral use [Link]
  11. Cayman Chemical: Thalidomide MSDS [Link]
  12. Health Canada Approved Drug Proucts: Thalidomid (thalidomide) capsules for oral use [Link]
Human Metabolome Database
HMDB0015175
KEGG Drug
D00754
KEGG Compound
C07910
PubChem Compound
5426
PubChem Substance
46505665
ChemSpider
5233
BindingDB
50070114
RxNav
10432
ChEBI
74947
ChEMBL
CHEMBL468
Therapeutic Targets Database
DAP000865
PharmGKB
PA451644
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Thalidomide
FDA label
Download (180 KB)
MSDS
Download (58.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentAnkylosing Spondylitis (AS)1
4CompletedTreatmentCutaneous Lupus / Juvenile SLE / Systemic Lupus Erythematosus1
4CompletedTreatmentMultiple Myeloma (MM)1
4Not Yet RecruitingTreatmentCamrelizumab / Lung Cancer1
4Not Yet RecruitingTreatmentHemodialysis Treatment / Thalidomide / Uremic Pruritus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Celgene
  • IDT Australia Ltd.
  • Penn Pharmaceutical Services Ltd.
Dosage Forms
FormRouteStrength
CapsuleOral
TabletOral100.000 mg
Tablet, film coatedOral100 mg
Tablet, coatedOral100 mg
CapsuleOral100 mg
CapsuleOral100 mg/1
CapsuleOral150 mg
CapsuleOral150 mg/1
CapsuleOral200 mg/1
CapsuleOral200 mg
CapsuleOral50 mg/1
CapsuleOral50 mg
Prices
Unit descriptionCostUnit
Thalomid 28 50 mg capsule Disp Pack4372.47USD disp
Thalomid 200 mg capsule277.5USD capsule
Thalomid 150 mg capsule260.61USD capsule
Thalomid 100 mg capsule243.73USD capsule
Thalomid 50 mg capsule150.15USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US6235756No2001-05-222013-03-01US flag
CA2505964No2009-07-282023-11-13Canada flag
CA2157288No2005-11-082014-02-24Canada flag
US6045501No2000-04-042018-08-28US flag
US6315720No2001-11-132020-10-23US flag
US6561976No2003-05-132018-08-28US flag
US6561977No2003-05-132020-10-23US flag
US6755784No2004-06-292020-10-23US flag
US6869399No2005-03-222020-10-23US flag
US6908432No2005-06-212018-08-28US flag
US7141018No2006-11-282020-10-23US flag
US7435745No2008-10-142017-11-03US flag
US7874984No2011-01-252018-08-28US flag
US7959566No2011-06-142020-10-23US flag
US8204763No2012-06-192018-08-28US flag
US8315886No2012-11-202020-10-23US flag
US8626531No2014-01-072020-10-23US flag
US8589188No2013-11-192018-08-28US flag
US7230012No2007-06-122023-12-09US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)270 °CPhysProp
water solubility545 mg/L (at 25 °C)BUDAVARI,S ET AL. (1996)
logP0.33HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility2.55 mg/mLALOGPS
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 Å2Chemaxon
Rotatable Bond Count1Chemaxon
Refractivity64.32 m3·mol-1Chemaxon
Polarizability24.42 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9775
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5651
P-glycoprotein substrateSubstrate0.5301
P-glycoprotein inhibitor INon-inhibitor0.5115
P-glycoprotein inhibitor IINon-inhibitor0.8951
Renal organic cation transporterNon-inhibitor0.8179
CYP450 2C9 substrateNon-substrate0.7904
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5309
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.9378
BiodegradationNot ready biodegradable0.8838
Rat acute toxicity3.3039 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9769
hERG inhibition (predictor II)Non-inhibitor0.8735
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-05d0-4950000000-f29254c7cc48a749c100
Mass Spectrum (Electron Ionization)MSsplash10-0wba-4900000000-77362eaf27267f59650d
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-1940000000-f6d6997d1eaa7a83ec1b
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-0930000000-e92e8e23d5db87f50f53
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0019-2900000000-ecfd1b7ec17b857ea977
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0930000000-e92e8e23d5db87f50f53
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-1940000000-f6d6997d1eaa7a83ec1b
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0019-2900000000-ecfd1b7ec17b857ea977
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0002-0930000000-13e39078e3b7c3388463
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-052b-0980000000-2662087743922855f299
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0890000000-30fe4d2107f121bf1159
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4j-1690000000-6a9c01d748fa98f0d01f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-3900000000-16bb9466e9660deaed65
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-8910000000-cf577995bbea1990daf0
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-164.9630183
predicted
DarkChem Lite v0.1.0
[M-H]-153.08026
predicted
DeepCCS 1.0 (2019)
[M+H]+165.3674183
predicted
DarkChem Lite v0.1.0
[M+H]+155.46243
predicted
DeepCCS 1.0 (2019)
[M+Na]+165.2130183
predicted
DarkChem Lite v0.1.0
[M+Na]+161.5314
predicted
DeepCCS 1.0 (2019)

Targets

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Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Metal ion binding
Specific Function
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2. Norma...
Gene Name
CRBN
Uniprot ID
Q96SW2
Uniprot Name
Protein cereblon
Molecular Weight
50545.375 Da
References
  1. Zhu YX, Kortuem KM, Stewart AK: Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma. Leuk Lymphoma. 2013 Apr;54(4):683-7. doi: 10.3109/10428194.2012.728597. Epub 2012 Sep 28. [Article]
Kind
Nucleotide
Organism
Humans
Pharmacological action
Yes
Actions
Intercalation
DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.
References
  1. Stephens TD, Bunde CJ, Fillmore BJ: Mechanism of action in thalidomide teratogenesis. Biochem Pharmacol. 2000 Jun 15;59(12):1489-99. [Article]
  2. Shoji A, Kuwahara M, Ozaki H, Sawai H: Modified DNA aptamer that binds the (R)-isomer of a thalidomide derivative with high enantioselectivity. J Am Chem Soc. 2007 Feb 7;129(5):1456-64. [Article]
  3. Stephens TD, Fillmore BJ: Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology. 2000 Mar;61(3):189-95. [Article]
  4. Koch HP, Czejka MJ: Evidence for the intercalation of thalidomide into DNA: clue to the molecular mechanism of thalidomide teratogenicity? Z Naturforsch C J Biosci. 1986 Nov-Dec;41(11-12):1057-61. [Article]
Kind
Protein group
Organism
Humans
Pharmacological action
Yes
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. Turk BE, Jiang H, Liu JO: Binding of thalidomide to alpha1-acid glycoprotein may be involved in its inhibition of tumor necrosis factor alpha production. Proc Natl Acad Sci U S A. 1996 Jul 23;93(15):7552-6. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Ando Y, Fuse E, Figg WD: Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Ando Y, Fuse E, Figg WD: Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73. [Article]
  2. Murayama N, van Beuningen R, Suemizu H, Guillouzo CG, Shibata N, Yajima K, Utoh M, Shimizu M, Chesne C, Nakamura M, Guengerich FP, Houtman R, Yamazaki H: Thalidomide increases human hepatic cytochrome P450 3A enzymes by direct activation of the pregnane X receptor. Chem Res Toxicol. 2014 Feb 17;27(2):304-308. doi: 10.1021/tx4004374. Epub 2014 Feb 5. [Article]
  3. Deeken JF, Cormier T, Price DK, Sissung TM, Steinberg SM, Tran K, Liewehr DJ, Dahut WL, Miao X, Figg WD: A pharmacogenetic study of docetaxel and thalidomide in patients with castration-resistant prostate cancer using the DMET genotyping platform. Pharmacogenomics J. 2010 Jun;10(3):191-9. doi: 10.1038/tpj.2009.57. Epub 2009 Dec 29. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Ando Y, Fuse E, Figg WD: Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Murayama N, van Beuningen R, Suemizu H, Guillouzo CG, Shibata N, Yajima K, Utoh M, Shimizu M, Chesne C, Nakamura M, Guengerich FP, Houtman R, Yamazaki H: Thalidomide increases human hepatic cytochrome P450 3A enzymes by direct activation of the pregnane X receptor. Chem Res Toxicol. 2014 Feb 17;27(2):304-308. doi: 10.1021/tx4004374. Epub 2014 Feb 5. [Article]
  2. Chowdhury G, Murayama N, Okada Y, Uno Y, Shimizu M, Shibata N, Guengerich FP, Yamazaki H: Human liver microsomal cytochrome P450 3A enzymes involved in thalidomide 5-hydroxylation and formation of a glutathione conjugate. Chem Res Toxicol. 2010 Jun 21;23(6):1018-24. doi: 10.1021/tx900367p. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Okada Y, Murayama N, Yanagida C, Shimizu M, Guengerich FP, Yamazaki H: Drug interactions of thalidomide with midazolam and cyclosporine A: heterotropic cooperativity of human cytochrome P450 3A5. Drug Metab Dispos. 2009 Jan;37(1):18-23. doi: 10.1124/dmd.108.024679. Epub 2008 Oct 23. [Article]
  2. Ando Y, Fuse E, Figg WD: Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res. 2002 Jun;8(6):1964-73. [Article]
  3. Li Y, Jiang Z, Xiao Y, Li L, Gao Y: Metabolism of thalidomide by human liver microsome cytochrome CYP2C19 is required for its antimyeloma and antiangiogenic activities in vitro. Hematol Oncol. 2012 Mar;30(1):13-21. doi: 10.1002/hon.992. Epub 2011 Jun 3. [Article]
  4. Ando Y, Price DK, Dahut WL, Cox MC, Reed E, Figg WD: Pharmacogenetic associations of CYP2C19 genotype with in vivo metabolisms and pharmacological effects of thalidomide. Cancer Biol Ther. 2002 Nov-Dec;1(6):669-73. doi: 10.4161/cbt.318. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Chowdhury G, Murayama N, Okada Y, Uno Y, Shimizu M, Shibata N, Guengerich FP, Yamazaki H: Human liver microsomal cytochrome P450 3A enzymes involved in thalidomide 5-hydroxylation and formation of a glutathione conjugate. Chem Res Toxicol. 2010 Jun 21;23(6):1018-24. doi: 10.1021/tx900367p. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48