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Identification
Name Lenalidomide
Accession Number DB00480 (APRD01303)
Type small molecule
Groups approved
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. [Wikipedia]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
CC-5013
CDC 501
IMiD3
Salts Not Available
Brand names
Name Company
Revimid
Revlimid
Revlimid (Celgene)
Brand mixtures Not Available
Categories
  • Antineoplastic Agents
CAS number 191732-72-6
Weight Average: 259.2606
Monoisotopic: 259.095691297
Chemical Formula C13H13N3O3
InChI Key InChIKey=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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Delta Lactams
  • Piperidines
  • Indoles and Indole Derivatives
  • Benzoyl Derivatives
  • Benzamides
Substructures
  • Delta Lactams
  • Carboxylic Acids and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Piperidines
  • Indoles and Indole Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Lactams
  • Benzoyl Derivatives
  • Benzamides
  • Anilines
  • Pyrrolines
Pharmacology
Indication For the treatment of patients with transfusion-dependent anemia due to low- or intermediate- risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
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.
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
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.
Volume of distribution Not Available
Protein binding 30%
Metabolism The metabolic profile of lenalidomide in humans has not been studied. In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion. The process exceeds the glomerular filtration rate and therefore is partially or entirely active.
Route of elimination In healthy volunteers, approximately two-thirds of lenalidomide is eliminated unchanged through urinary excretion.
Half life 3 hours
Clearance Not Available
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
Pharmacoeconomics
Manufacturers
  • Celgene corp
  • Celgene Corporation
Packagers
Dosage forms Not Available
Prices
Unit description Cost Unit
Revlimid 25 mg capsule 411.71 USD capsule
Revlimid 15 mg capsule 407.7 USD capsule
Revlimid 10 mg capsule 406.05 USD capsule
Revlimid 5 mg capsule 388.0 USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 7465800 2006-04-22 2026-04-22
United States 6281230 1996-07-24 2016-07-24
Canada 2477301 2009-09-01 2023-04-13
Canada 2342974 2005-08-16 2014-02-24
Properties
State solid
Experimental Properties
Property Value Source
water solubility Soluble 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 -0.4 Not Available
Predicted Properties
Property Value Source
water solubility 2.33e+00 g/l ALOGPS
logP -0.43 ALOGPS
logP -0.71 ChemAxon
logS -2 ALOGPS
pKa (strongest acidic) 11.61 ChemAxon
pKa (strongest basic) 2.31 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 92.5 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 68.3 ChemAxon
polarizability 25.55 ChemAxon
References
Synthesis Reference Not Available
General Reference
  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
  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
  3. Anderson KC: Lenalidomide and thalidomide: mechanisms of action—similarities and differences. Semin Hematol. 2005 Oct;42(4 Suppl 4):S3-8. Pubmed
External Links
Resource Link
KEGG Drug D04687 Link_out
PubChem Compound 216326 Link_out
PubChem Substance 46505725 Link_out
ChemSpider 187515 Link_out
BindingDB 50078323 Link_out
Therapeutic Targets Database DAP001255 Link_out
PharmGKB PA162363968 Link_out
Drugs.com http://www.drugs.com/cdi/lenalidomide.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Lenalidomide Link_out
ATC Codes
  • L04AX04
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (400 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Trastuzumab Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Food Interactions Not Available
Targets

1. Tumor necrosis factor ligand superfamily member 11

Pharmacological action: yes
Actions: inhibitor

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 an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy

Organism class: human
UniProt ID: O14788 Link_out
Gene: TNFSF11
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  2. Melchert M, List A: The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. Epub 2007 Jan 30. Pubmed

2. Cadherin-5

Pharmacological action: unknown
Actions: antagonist

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 heterogeneous cell types. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions. It associates with alpha-catenin forming a link to the cytoskeleton

Organism class: human
UniProt ID: P33151 Link_out
Gene: CDH5
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Sep 4. Pubmed

3. Vascular endothelial growth factor

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: A2A2V4 Link_out
Gene: VEGF Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Sep 4. Pubmed

4. Prostaglandin G/H synthase 2

Pharmacological action: unknown
Actions: negative modulator

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19