Identification

Name
Lenalidomide
Accession Number
DB00480
Description

Lenalidomide (initially known as CC-5013 and marketed as Revlimid® by Celgene) is a derivative of thalidomide introduced in 2004. It was initially intended as a treatment for multiple myeloma, for which thalidomide is an accepted therapeutic modality, but has also shown efficacy in the hematological disorders known as the myelodysplastic syndromes. FDA approved on December 27, 2005.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 259.2606
Monoisotopic: 259.095691297
Chemical Formula
C13H13N3O3
Synonyms
  • 1-oxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline
  • 3-(4-Amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione
  • Lenalidomida
  • Lenalidomide
External IDs
  • CC-5013
  • CDC 501
  • CDC-501
  • ENMD 0997
  • SYP-1512

Pharmacology

Indication

Lenalidomide is indicated for the treatment of multiple myeloma in combination with dexamethasone. It is also indicated for the treatment of patients with transfusion-dependent anemia due to low- or intermediate- risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Lenalidomide, a thalidomide analogue, is an immunomodulatory agent possessing immunomodulatory and antiangiogenic properties. Lenalidomide inhibits the secretion of pro-inflammatory cytokines and increases the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide inhibits cell proliferation with varying effectiveness (IC50s) in some but not all cell lines. Lenalidomide is effective in inhibiting growth of Namalwa cells (a human B cell lymphoma cell line with a deletion of one chromosome 5) but is much less effective in inhibiting growth of KG-1 cells (human myeloblastic cell line, also with a deletion of one chromosome 5) and other cell lines without chromosome 5 deletions. Lenalidomide does not prolong the QTc interval.

Mechanism of action

The mechanism of action of lenalidomide remains to be fully characterized, however it has been demonstrated that lenalidomide inhibits the expression of cyclooxygenase-2 (COX-2), but not COX-1, in vitro. In vivo it induces tumor cell apoptosis directly and indirectly by inhibition of bone marrow stromal cell support, by anti-angiogenic and anti-osteoclastogenic effects, and by immunomodulatory activity

TargetActionsOrganism
AProtein cereblon
inhibitor
Humans
ATumor necrosis factor ligand superfamily member 11
inhibitor
Humans
UCadherin-5
antagonist
Humans
UProstaglandin G/H synthase 2
negative modulator
Humans
Absorption

Rapidly absorbed following oral administration, with maximum plasma concentrations occurring between 0.625 and 1.5 hours post-dose. Co-administration with food does not alter the extent of absorption (AUC) but does reduce the maximal plasma concentration (Cmax) by 36%. The pharmacokinetic disposition of lenalidomide is linear. Accumulation does not occur following multiple doses.

Volume of distribution
Not Available
Protein binding

30% protein bound.

Metabolism

Lenalidomide undergoes limited metabolism. Unchanged lenalidomide is the predominant circulating component in humans. Two identified metabolites are hydroxy-lenalidomide and N-acetyl-lenalidomide; each constitutes less than 5% of parent levels in circulation. The cytochrome P450 enzyme system is not involved with the metabolism of lenalidomide.

Route of elimination

Elimination is primarily renal. When a single oral dose of 25 mg is given healthy subjects, 90% and 4% of the dose is eliminated in urine and feces, respectively. Hydroxy-lenalidomide and N-acetyl-lenalidomide represent 4.59% and 1.83% of the excreted dose, respectively.

Half-life

Healthy subjects = 3 hours; Multiple myeloma or MDS patients = 3 - 5 hours.

Clearance

The renal clearance of lenalidomide exceeds the glomerular filtration rate.

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

The most frequently reported adverse events were related to blood and lymphatic system disorders, skin and subcutaneous tissue disorders, gastrointestinal disorders, and general disorders and administrative site conditions.

Affected organisms
  • Humans and other mammals
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
AbacavirLenalidomide may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbataceptThe risk or severity of adverse effects can be increased when Lenalidomide is combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Lenalidomide.
AcarboseAcarbose may decrease the excretion rate of Lenalidomide which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Lenalidomide which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Lenalidomide which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Acenocoumarol is combined with Lenalidomide.
AcetaminophenAcetaminophen may decrease the excretion rate of Lenalidomide which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Lenalidomide which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Lenalidomide which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. High-fat meals decrease absorption, but not to a clinically significant extent.

Products

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International/Other Brands
Ladevina / Lenangio
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RevlimidCapsule15 mgOralCelgene2008-10-10Not applicableCanada flag
RevlimidCapsule25 mgOralCelgene Europe Limited2007-06-14Not applicableEU flag
RevlimidCapsule25 mg/1OralCelgene Corporation2006-06-29Not applicableUS flag
RevlimidCapsule10 mg/1OralCelgene Corporation2005-12-27Not applicableUS flag
RevlimidCapsule5 mgOralCelgene Europe Limited2007-06-14Not applicableEU flag
RevlimidCapsule20 mgOralCelgene2015-09-28Not applicableCanada flag
RevlimidCapsule20 mgOralCelgene Europe Limited2007-06-14Not applicableEU flag
RevlimidCapsule7.5 mgOralCelgene Europe Limited2007-06-14Not applicableEU flag
RevlimidCapsule10 mgOralCelgene2008-02-19Not applicableCanada flag
RevlimidCapsule15 mgOralCelgene Europe Limited2007-06-14Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
L04AX04 — Lenalidomide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as isoindolones. These are aromatic polycyclic compounds that an isoindole bearing a ketone.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Isoindoles and derivatives
Sub Class
Isoindolines
Direct Parent
Isoindolones
Alternative Parents
Alpha amino acids and derivatives / Isoindoles / Piperidinediones / Delta lactams / Benzenoids / Tertiary carboxylic acid amides / N-unsubstituted carboxylic acid imides / Dicarboximides / Azacyclic compounds / Primary amines
show 4 more
Substituents
Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Carboxylic acid imide
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dicarboximide, aromatic amine, piperidones, isoindoles (CHEBI:63791)

Chemical Identifiers

UNII
F0P408N6V4
CAS number
191732-72-6
InChI Key
GOTYRUGSSMKFNF-UHFFFAOYSA-N
InChI
InChI=1S/C13H13N3O3/c14-9-3-1-2-7-8(9)6-16(13(7)19)10-4-5-11(17)15-12(10)18/h1-3,10H,4-6,14H2,(H,15,17,18)
IUPAC Name
3-(4-amino-1-oxo-2,3-dihydro-1H-isoindol-2-yl)piperidine-2,6-dione
SMILES
NC1=CC=CC2=C1CN(C1CCC(=O)NC1=O)C2=O

References

Synthesis Reference

Surya Narayana Devarakonda, Sesha Reddy Yarraguntla, Vamsi Krishna Mudapaka, Rajasekhar Kadaboina, Veerender Murki, Amarendhar Manda, Venkata Rao Badisa, Naresh Vemula, Rama Seshagiri Rao Pulla, Venu Nalivela, "PREPARATION OF LENALIDOMIDE." U.S. Patent US20110021567, issued January 27, 2011.

US20110021567
General References
  1. List A, Kurtin S, Roe DJ, Buresh A, Mahadevan D, Fuchs D, Rimsza L, Heaton R, Knight R, Zeldis JB: Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005 Feb 10;352(6):549-57. [PubMed:15703420]
  2. Chang DH, Liu N, Klimek V, Hassoun H, Mazumder A, Nimer SD, Jagannath S, Dhodapkar MV: Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications. Blood. 2006 Jul 15;108(2):618-21. Epub 2006 Mar 28. [PubMed:16569772]
  3. Anderson KC: Lenalidomide and thalidomide: mechanisms of action--similarities and differences. Semin Hematol. 2005 Oct;42(4 Suppl 4):S3-8. [PubMed:16344099]
Human Metabolome Database
HMDB0014623
KEGG Drug
D04687
PubChem Compound
216326
PubChem Substance
46505725
ChemSpider
187515
BindingDB
65454
RxNav
342369
ChEBI
63791
ChEMBL
CHEMBL848
Therapeutic Targets Database
DAP001255
PharmGKB
PA162363968
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Lenalidomide
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
FDA label
Download (400 KB)
MSDS
Download (225 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentMultiple Myeloma (MM)1
4Active Not RecruitingTreatmentRelapsed and/or Refractory Multiple Myeloma1
4CompletedTreatmentCutaneous Lupus1
4CompletedTreatmentMultiple Myeloma (MM)1
4Not Yet RecruitingTreatmentNovel Coronavirus Infectious Disease (COVID-19)1
4RecruitingTreatmentMultiple Myeloma (MM)3
4RecruitingTreatmentNewly Diagnosed Multiple Myeloma1
4RecruitingTreatmentNK/T Cell Lymphoma1
4RecruitingTreatmentPeripheral T-Cell Lymphoma (PTCL)1
4RecruitingTreatmentRelapsed Or Refractory Multiple Myeloma1

Pharmacoeconomics

Manufacturers
  • Celgene corp
  • Celgene Corporation
Packagers
  • Celgene
  • Norwich Pharmaceuticals Inc.
  • Penn Pharmaceutical Services Ltd.
Dosage Forms
FormRouteStrength
Capsule, coatedOral10 mg
Capsule, coatedOral15 mg
Capsule, coatedOral25 mg
Capsule, coatedOral5 mg
CapsuleOral10 mg/1
CapsuleOral10 mg
CapsuleOral15 mg
CapsuleOral15 mg/1
CapsuleOral2.5 mg
CapsuleOral2.5 mg/1
CapsuleOral20 mg/1
CapsuleOral20 mg
CapsuleOral25 mg
CapsuleOral25 mg/1
CapsuleOral5 mg
CapsuleOral5 mg/1
CapsuleOral7.5 mg
Prices
Unit descriptionCostUnit
Revlimid 25 mg capsule411.71USD capsule
Revlimid 15 mg capsule407.7USD capsule
Revlimid 10 mg capsule406.05USD capsule
Revlimid 5 mg capsule388.0USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2477301No2009-09-012023-04-13Canada flag
CA2342974No2005-08-162014-02-24Canada 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
US6908432No2005-06-212018-08-28US 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
US7468363No2008-12-232023-10-07US flag
US6281230No2001-08-282016-07-24US flag
US8530498No2013-09-102023-05-15US flag
US6555554No2003-04-292016-07-24US flag
US7189740No2007-03-132023-04-11US flag
US7968569No2011-06-282023-10-07US flag
US8404717No2013-03-262023-04-11US flag
US8648095No2014-02-112023-05-15US flag
US8741929No2014-06-032028-03-08US flag
US9101622No2015-08-112023-05-15US flag
US9101621No2015-08-112023-05-15US flag
US9056120No2015-06-162023-04-11US flag
US5635517No1997-06-032019-10-04US flag
US7119106No2006-10-102016-07-24US flag
US7465800No2008-12-162027-04-27US flag
US7855217No2010-12-212024-11-24US flag
US8288415No2012-10-162016-07-24US flag
US9393238No2016-07-192023-05-15US flag
US8492406No2013-07-232023-10-07US flag
US9155730No2015-10-132023-05-15US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySoluble in organic solvent/water mixtures, and buffered aqueous solvents. Lenalidomide is more soluble in organic solvents and low pH solutions. Solubility was significantly lower in less acidic buffers, ranging from about 0.4 to 0.5 mg/mL.Not Available
logP-0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.33 mg/mLALOGPS
logP-0.43ALOGPS
logP-0.71ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)11.61ChemAxon
pKa (Strongest Basic)2.31ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area92.5 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity68.3 m3·mol-1ChemAxon
Polarizability25.55 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.9372
Caco-2 permeable-0.5981
P-glycoprotein substrateSubstrate0.6845
P-glycoprotein inhibitor IInhibitor0.6012
P-glycoprotein inhibitor IINon-inhibitor0.8927
Renal organic cation transporterNon-inhibitor0.726
CYP450 2C9 substrateNon-substrate0.8861
CYP450 2D6 substrateNon-substrate0.7878
CYP450 3A4 substrateSubstrate0.5855
CYP450 1A2 substrateNon-inhibitor0.8746
CYP450 2C9 inhibitorNon-inhibitor0.8405
CYP450 2D6 inhibitorNon-inhibitor0.8806
CYP450 2C19 inhibitorNon-inhibitor0.78
CYP450 3A4 inhibitorNon-inhibitor0.7469
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.843
Ames testNon AMES toxic0.8268
CarcinogenicityNon-carcinogens0.9068
BiodegradationNot ready biodegradable0.9967
Rat acute toxicity2.5145 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9803
hERG inhibition (predictor II)Non-inhibitor0.5098
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-1920000000-c10c48acd9b8123e3505

Targets

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. [PubMed:22966948]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Tumor necrosis factor receptor superfamily binding
Specific Function
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be...
Gene Name
TNFSF11
Uniprot ID
O14788
Uniprot Name
Tumor necrosis factor ligand superfamily member 11
Molecular Weight
35477.81 Da
References
  1. Akobeng AK, Stokkers PC: Thalidomide and thalidomide analogues for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD007351. doi: 10.1002/14651858.CD007351.pub2. [PubMed:19370685]
  2. Melchert M, List A: The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. Epub 2007 Jan 30. [PubMed:17369076]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor binding
Specific Function
Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of hete...
Gene Name
CDH5
Uniprot ID
P33151
Uniprot Name
Cadherin-5
Molecular Weight
87527.715 Da
References
  1. Lu L, Payvandi F, Wu L, Zhang LH, Hariri RJ, Man HW, Chen RS, Muller GW, Hughes CC, Stirling DI, Schafer PH, Bartlett JB: The anti-cancer drug lenalidomide inhibits angiogenesis and metastasis via multiple inhibitory effects on endothelial cell function in normoxic and hypoxic conditions. Microvasc Res. 2009 Mar;77(2):78-86. doi: 10.1016/j.mvr.2008.08.003. Epub 2008 Sep 4. [PubMed:18805433]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Negative modulator
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. Payvandi F, Wu L, Haley M, Schafer PH, Zhang LH, Chen RS, Muller GW, Stirling DI: Immunomodulatory drugs inhibit expression of cyclooxygenase-2 from TNF-alpha, IL-1beta, and LPS-stimulated human PBMC in a partially IL-10-dependent manner. Cell Immunol. 2004 Aug;230(2):81-8. [PubMed:15598423]
  2. Zeldis JB, Schafer PH, Bennett BL, Mercurio F, Stirling DI: Potential new therapeutics for Waldenstrom's macroglobulinemia. Semin Oncol. 2003 Apr;30(2):275-81. [PubMed:12720152]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da

Drug created on June 13, 2005 07:24 / Updated on November 30, 2020 13:38

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