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A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, thalidomide was withdrawn from the market due to teratogenic effects.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Approved, Investigational, Withdrawn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

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Thalidomide (DB01041)

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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

• Chronic Graft Versus Host Disease
• Erythema Nodosum Leprosum
• Light-Chain Amyloidosis
• Multiple Myeloma (MM)
• Stomatitis, Aphthous
• Uremic Pruritus
• Waldenström's Macroglobulinemia (WM)
• Moderate Erythema nodosum leprosum
• Refractory Graft versus host disease
• Severe Erythema nodosum leprosum
• Treatment naive multiple myeloma

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

Target	Actions	Organism
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 (T_max) 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 t_lag 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, c_max 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

Hover over products below to view reaction partners

• Thalidomide
  • cis, trans-5'-Hydroxythalidomide
    • cis,trans-5,5’-dihydroxythalidomide
  • Thalidomide arene oxide
    • 5-Hydroxythalidomide
  • 4-phthalimidoglutaramic acid
    • 4-(o-carboxybenzamido)glutaramic acid
      • Isoglutamine + Phthalic Acid
      • 2-(o-carboxybenzamido)glutaric acid
        • Glutamic acid + Phthalic Acid
    • 2-phthalimidoglutaric acid
      • 2-(o-carboxybenzamido)glutaric acid
        • Glutamic acid + Phthalic Acid
  • 2-phthalimidoglutaramic acid
    • 2-(o-carboxybenzamido)glutaramic acid
      • L-Glutamine + Phthalic Acid
      • 2-(o-carboxybenzamido)glutaric acid
        • Glutamic acid + Phthalic Acid
    • 2-phthalimidoglutaric acid
      • 2-(o-carboxybenzamido)glutaric acid
        • Glutamic acid + Phthalic Acid
  • alpha-(o-carboxybenzamido)glutarimide
    • 2-(o-carboxybenzamido)glutaramic acid
      • 2-(o-carboxybenzamido)glutaric acid
        • Glutamic acid + Phthalic Acid
      • L-Glutamine + Phthalic Acid
    • Phthalic Acid + alpha-aminoglutarimide
  • 5-Hydroxythalidomide
    • cis,trans-5,5’-dihydroxythalidomide
    • 5,6-dihydroxythalidomide
  • Thalidomide-5-O-glucuronide
  • N-Hydroxythalidomide
  • 4-hydroxythalidomide

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Abatacept	The metabolism of Thalidomide can be increased when combined with Abatacept.
Abciximab	The risk or severity of bleeding can be increased when Abciximab is combined with Thalidomide.
Abrocitinib	The metabolism of Abrocitinib can be decreased when combined with Thalidomide.
Acebutolol	The risk or severity of adverse effects can be increased when Thalidomide is combined with Acebutolol.
Acenocoumarol	The risk or severity of bleeding can be increased when Thalidomide is combined with Acenocoumarol.
Acetazolamide	Acetazolamide may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Acetohexamide	The metabolism of Thalidomide can be decreased when combined with Acetohexamide.
Acetophenazine	Acetophenazine may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Acetyl sulfisoxazole	The metabolism of Thalidomide can be decreased when combined with Acetyl sulfisoxazole.

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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

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Thalidomide Celgene	Capsule	50 mg	Oral	Bristol Myers Squibb Pharma Eeig	2016-09-08	Not applicable
Thalidomide Lipomed	Tablet, coated	100 mg	Oral	Lipomed	2022-12-02	Not applicable
Thalomid	Capsule	50 mg/1	Oral	Celgene Corporation	2003-06-20	Not applicable
Thalomid	Capsule	200 mg	Oral	Celgene	2011-02-17	Not applicable
Thalomid	Capsule	150 mg/1	Oral	Celgene Corporation	2007-03-20	Not applicable
Thalomid	Capsule	50 mg	Oral	Celgene	2010-11-01	Not applicable
Thalomid	Capsule	100 mg	Oral	Celgene	2011-02-17	Not applicable
Thalomid	Capsule	100 mg/1	Oral	Celgene Corporation	2003-06-20	Not applicable
Thalomid	Capsule	150 mg	Oral	Celgene	Not applicable	Not applicable
Thalomid	Capsule	200 mg/1	Oral	Celgene Corporation	2003-06-20	Not applicable

Categories

ATC Codes

L04AX02 — Thalidomide

• L04AX — Other immunosuppressants
• L04A — IMMUNOSUPPRESSANTS
• L04 — IMMUNOSUPPRESSANTS
• L — ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS

Drug Categories

• Acids, Carbocyclic
• Angiogenesis Inhibitors
• Angiogenesis Modulating Agents
• Anti-Bacterial Agents
• Anti-Infective Agents
• Antineoplastic Agents
• Antineoplastic and Immunomodulating Agents
• Cardiotoxic antineoplastic agents
• Central Nervous System Depressants
• Cytochrome P-450 CYP2B6 Inducers
• Cytochrome P-450 CYP2B6 Inducers (strength unknown)
• Cytochrome P-450 CYP2B6 Substrates
• Cytochrome P-450 CYP2C19 Inhibitors
• Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
• Cytochrome P-450 CYP2C19 Substrates
• Cytochrome P-450 CYP2C9 Substrates
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (strength unknown)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Inducers
• Cytochrome P-450 CYP3A5 Inducers (strength unknown)
• Cytochrome P-450 CYP3A5 Substrates
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Decreased Immunologically Active Molecule Activity
• Drugs causing inadvertant photosensitivity
• Growth Inhibitors
• Growth Substances
• Heterocyclic Compounds, Fused-Ring
• Hypotensive Agents
• Immunologic Factors
• Immunomodulatory Agents
• Immunosuppressive Agents
• Isoindoles
• Leprostatic Agents
• Myelosuppressive Agents
• Noxae
• Photosensitizing Agents
• Phthalic Acids
• Phthalimides
• Piperidines
• Piperidones
• Teratogens
• Toxic Actions
• Tumor Necrosis Factor Blockers

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 / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl 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 / Dicarboximide / Hydrocarbon derivative / Isoindole / Lactam / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Phthalimide / Piperidine / Piperidinedione / Piperidinone

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]

External Links

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

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Cutaneous Lupus / Juvenile SLE / Systemic Lupus Erythematosus (SLE)	1
4	Completed	Treatment	Multiple Myeloma (MM)	1
4	Not Yet Recruiting	Treatment	Cancer, Therapy-Related	1
4	Not Yet Recruiting	Treatment	Hemodialysis Treatment / Thalidomide / Uremic Pruritus	1
4	Recruiting	Treatment	Ankylosing Spondylitis (AS)	1
4	Recruiting	Treatment	Immunoglobulin Light-Chain Amyloidosis	1
4	Terminated	Treatment	Uveitis	1
4	Unknown Status	Treatment	Congestive Heart Failure (CHF)	1
4	Unknown Status	Treatment	Coronary Artery Disease (CAD)	1
4	Unknown Status	Treatment	Malignant Neoplasm of Stomach	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

• Celgene
• IDT Australia Ltd.
• Penn Pharmaceutical Services Ltd.

Dosage Forms

Form	Route	Strength
Capsule	Oral
Tablet, film coated	Oral	100 mg
Tablet, coated	Oral	100 mg
Capsule	Oral	100 mg
Capsule	Oral	100 mg/1
Capsule	Oral	150 mg
Capsule	Oral	150 mg/1
Capsule	Oral	200 mg
Capsule	Oral	200 mg/1
Capsule	Oral	50 mg/1
Capsule	Oral	50 mg

Prices

Unit description	Cost	Unit
Thalomid 28 50 mg capsule Disp Pack	4372.47USD	disp
Thalomid 200 mg capsule	277.5USD	capsule
Thalomid 150 mg capsule	260.61USD	capsule
Thalomid 100 mg capsule	243.73USD	capsule
Thalomid 50 mg capsule	150.15USD	capsule

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US6235756	No	2001-05-22	2013-03-01
CA2505964	No	2009-07-28	2023-11-13
CA2157288	No	2005-11-08	2014-02-24
US6045501	No	2000-04-04	2018-08-28
US6315720	No	2001-11-13	2020-10-23
US6561976	No	2003-05-13	2018-08-28
US6561977	No	2003-05-13	2020-10-23
US6755784	No	2004-06-29	2020-10-23
US6869399	No	2005-03-22	2020-10-23
US6908432	No	2005-06-21	2018-08-28
US7141018	No	2006-11-28	2020-10-23
US7435745	No	2008-10-14	2017-11-03
US7874984	No	2011-01-25	2018-08-28
US7959566	No	2011-06-14	2020-10-23
US8204763	No	2012-06-19	2018-08-28
US8315886	No	2012-11-20	2020-10-23
US8626531	No	2014-01-07	2020-10-23
US8589188	No	2013-11-19	2018-08-28
US7230012	No	2007-06-12	2023-12-09

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	270 °C	PhysProp
water solubility	545 mg/L (at 25 °C)	BUDAVARI,S ET AL. (1996)
logP	0.33	HANSCH,C ET AL. (1995)

Predicted Properties

Property	Value	Source
Water Solubility	2.55 mg/mL	ALOGPS
logP	0.42	ALOGPS
logP	0.016	Chemaxon
logS	-2	ALOGPS
pKa (Strongest Acidic)	11.59	Chemaxon
pKa (Strongest Basic)	-6.4	Chemaxon
Physiological Charge	0	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	83.55 Å2	Chemaxon
Rotatable Bond Count	1	Chemaxon
Refractivity	64.32 m3·mol-1	Chemaxon
Polarizability	24.42 Å3	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.9775
Blood Brain Barrier	+	0.9382
Caco-2 permeable	-	0.5651
P-glycoprotein substrate	Substrate	0.5301
P-glycoprotein inhibitor I	Non-inhibitor	0.5115
P-glycoprotein inhibitor II	Non-inhibitor	0.8951
Renal organic cation transporter	Non-inhibitor	0.8179
CYP450 2C9 substrate	Non-substrate	0.7904
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Substrate	0.5309
CYP450 1A2 substrate	Non-inhibitor	0.9045
CYP450 2C9 inhibitor	Non-inhibitor	0.9071
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.8682
Ames test	Non AMES toxic	0.9133
Carcinogenicity	Non-carcinogens	0.9378
Biodegradation	Not ready biodegradable	0.8838
Rat acute toxicity	3.3039 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9769
hERG inhibition (predictor II)	Non-inhibitor	0.8735

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-0wba-4900000000-77362eaf27267f59650d
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-qTof , Positive	LC-MS/MS	Not Available
MS/MS Spectrum - , positive	LC-MS/MS	splash10-000i-0930000000-e92e8e23d5db87f50f53
MS/MS Spectrum - , positive	LC-MS/MS	splash10-000i-1940000000-f6d6997d1eaa7a83ec1b
MS/MS Spectrum - , positive	LC-MS/MS	splash10-0019-2900000000-ecfd1b7ec17b857ea977

Targets

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Details1. Protein cereblon

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]

Details2. DNA

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]

Details3. alpha1-acid glycoprotein (Protein Group)

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:

Name	UniProt ID
Alpha-1-acid glycoprotein 1	P02763
Alpha-1-acid glycoprotein 2	P19652

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]

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Drug created at June 13, 2005 13:24 / Updated at December 08, 2022 17:54