Explore a selection of our essential drug information below, or:
Identification
- Summary
Lenalidomide is a thalidomide derivative used to treat multiple myeloma and anemia in low to intermediate risk myelodysplastic syndrome.
- Brand Names
- Revlimid
- Generic Name
- Lenalidomide
- DrugBank Accession Number
- DB00480
- Background
Lenalidomide (previously referred to as CC-5013) is an immunomodulatory drug with potent antineoplastic, anti-angiogenic, and anti-inflammatory properties.4 It is a 4-amino-glutamyl analogue of thalidomide 3 and like thalidomide, lenalidomide exists as a racemic mixture of the active S(-) and R(+) forms.7 However, lenalidomide is much safer and potent than thalidomide, with fewer adverse effects and toxicities.2,3 Thalidomide and its analogues, including lenalidomide, are referred to as immunomodulatory imide drugs (also known as cereblon modulators), which are a class of immunomodulatory drugs that contain an imide group. Lenalidomide works through various mechanisms of actions that promote malignant cell death and enhance host immunity.7 Available as oral capsules, lenalidomide is approved by the FDA and EU for the treatment of multiple myeloma, myelodysplastic syndromes, mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma in selected patients.9 Due to severe teratogenicity, pregnancy must be excluded before the start of treatment and patients must enroll in the lenalidomide Risk Evaluation and Mitigation Strategy (REMS) program to ensure contraception adherence.7
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Lenalidomide (DB00480)
- 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 adult patients with multiple myeloma (MM) in combination with dexamethasone. It is also indicated as maintenance therapy in multiple myeloma following autologous hematopoietic stem cell transplantation (auto-HSCT).
It is indicated for the treatment of adult patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities.
Lenalidomide is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.
In combination with a rituximab product, lenalidomide is indicated for the treatment of adult patients with previously treated follicular lymphoma (FL) or previously treated marginal zone lymphoma (MZL).9
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Follicular lymphoma (fl) Regimen in combination with: Rituximab (DB00073) •••••••••••• ••••• •••••••••• ••••••• ••••••• Treatment of Light-chain amyloidosis ••• ••••• Treatment of Mantle cell lymphoma •••••••••••• ••••• •••••••• •••••• •••••••••• ••••••••• •• ••••• ••• ••••• •••••••• •••••••••••• •••••••• ••••••• Used in combination to treat Marginal zone lymphoma (mzl) Regimen in combination with: Rituximab (DB00073) •••••••••••• ••••• •••••••••• ••••••• ••••••• Used in combination to treat Multiple myeloma Regimen in combination with: Dexamethasone (DB01234) •••••••••••• ••••• ••••••••••••••• ••••••••••••• •••• •••• ••••••••••••••• ••••••• - Contraindications & Blackbox Warnings
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In hematological malignancies, the immune system is deregulated in the form of altered cytokine networks in the tumour microenvironment, defective T cell regulation of host-tumour immune interactions, and diminished NK cell activity.3 Lenalidomide is an immunomodulatory agent with antineoplastic, antiangiogenic, and anti-inflammatory properties.5 Lenalidomide exerts direct cytotoxicity by increasing apoptosis and inhibiting the proliferation of hematopoietic malignant cells.7 It delays tumour growth in nonclinical hematopoietic tumour models in vivo, including multiple myeloma.9 Lenalidomide also works to limit the invasion or metastasis of tumour cells and inhibits angiogenesis.7
Lenalidomide also mediates indirect antitumour effects via its immunomodulatory actions: it inhibits the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies. Lenalidomide enhances the host immunity by stimulating T cell proliferation and enhancing the activity of natural killer (NK) cells.1,6,7 Lenalidomide is about 100–1000 times more potent in stimulating T cell proliferation than thalidomide.3 In vitro, it enhances antibody-dependent cell-mediated cytotoxicity (ADCC), which is even more pronounced when used in combination with rituximab.9 Due to its anti-inflammatory properties, lenalidomide has been investigated in the context of inflammatory and autoimmune diseases, such as amyotrophic lateral sclerosis.8
- Mechanism of action
Lenalidomide is a drug with multiple mechanisms of action. Lenalidomide exerts immunomodulating effects by altering cytokine production, regulating T cell co-stimulation, and enhancing the NK cell-mediated cytotoxicity.3 Lenalidomide directly inhibits the cullin ring E3 ubiquitin ligase complex: upon binding to cereblon, a substrate adaptor of the complex, lenalidomide modulates substrate specificity of the complex to recruit substrate proteins of the ligase, including Ikaros (IKZF1), Aiolos (IKZF3), and CK1α.9 These substrates are then tagged for ubiquitination and subsequent proteasomal degradation. IKZF1 and IKZF3 are B-cell transcription factors that are essential for B-cell differentiation and survival of malignant cells. IKZF3 also regulates the expression of interferon regulatory factor 4 (IRF4), which is a transcription factor that regulates the aberrant myeloma-specific gene. The immunomodulatory actions of lenalidomide can be partly explained by the degradation of IKZF3, since it is a repressor of the interleukin 2 gene (IL2): as lenalidomide decreases the level of IKZF3, the production of IL-2 increases, thereby increasing the proliferation of natural killer (NK), NKT cells, and CD4+ T cells.6 Lenalidomide inhibits the production of pro-inflammatory cytokines TNF-α, IL-1, IL-6, and IL-12, while elevating the production of anti-inflammatory cytokine IL-10.3 Lenalidomide acts as a T-cell co-stimulatory molecule that promotes CD3 T-cell proliferation and increases the production of IL-2 and IFN-γ in T lymphocytes, which enhances NK cell cytotoxicity and ADCC. It inhibits the expression and function of T-regulatory cells, which are often overabundant in some hematological malignancies.7
Lenalidomide directly exerts antitumour effects by inhibiting the proliferation and inducing apoptosis of tumour cells. Lenalidomide triggers the activation of pro-apoptotic caspase-8, enhances tumour cell sensitivity to FAS-induced apoptosis, and downregulates NF-κB, an anti-apoptotic protein.7 Independent of its immunomodulatory effects, lenalidomide mediates anti-angiogenic effects by inhibiting angiogenic growth factors released by tumour cells, such as vascular endothelial growth factor (VEGF), basic fibroblastic-growth factor (BFGF), and hepatocyte-growth factor. In vitro, lenalidomide inhibits cell adhesion molecules such as ICAM-1, LFA-1, β2 and β3 integrins, as well as gap-junction function, thereby preventing metastasis of malignant cells.7
Target Actions Organism ATumor necrosis factor inhibitorHumans AProtein cereblon inhibitorHumans ATumor necrosis factor ligand superfamily member 11 inhibitorHumans UCadherin-5 antagonistHumans UProstaglandin G/H synthase 2 negative modulatorHumans - Absorption
Following oral administration, lenalidomide is rapidly absorbed with high bioavailability.5 It has a Tmax ranging from 0.5 to six hours. Lenalidomide exhibits a linear pharmacokinetic profile, with its AUC and Cmax increasing proportionally with dose. Multiple dosing does not result in drug accumulation.9 In healthy male subjects, the Cmax was 413 ± 77 ng/ml and the AUCinfinity was 1319 ± 162 h x ng/ml.5
- Volume of distribution
In healthy male subjects, the apparent volume of distribution was 75.8 ± 7.3 L.5
- Protein binding
In vitro, about 30% of lenalidomide was bound to plasma proteins.9
- Metabolism
Lenalidomide is not subject to extensive hepatic metabolism involving CYP enzymes and metabolism contributes to a very minor extent to the clearance of lenalidomide in humans. Lenalidomide undergoes hydrolysis in human plasma to form 5-hydroxy-lenalidomide and N-acetyl-lenalidomide.5 Unchanged lenalidomide is the predominant circulating drug form, with metabolites accounting for less than five percent of the parent drug levels in the circulation.9
Hover over products below to view reaction partners
- Route of elimination
Lenalidomide is eliminated predominantly via urinary excretion in the unchanged form. Following oral administration of 25 mg of radiolabeled lenalidomide in healthy subjects, about 90% of the dose (4.59% as metabolites) was eliminated in urine and 4% of the dose (1.83% as metabolites) was eliminated in feces within ten days post-dose. Approximately 85% of the dose was excreted as lenalidomide in the urine within 24 hours.9
- Half-life
In healthy subjects, the mean half-life of lenalidomide is three hours in the clinically relevant dose range (5–50 mg).5 Half-life can range from three to five hours in patients with multiple myeloma, myelodysplastic syndromes, or mantle cell lymphoma.9
- Clearance
The renal clearance of lenalidomide exceeds the glomerular filtration rate.9 In healthy male subjects, the oral clearance was 318 ± 41 mL/min.5
- Adverse Effects
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The lowest lethal dose (LDLo) in rats is >2000 mg/kg following oral administration and >40 mg/kg following intravenous administration.10 The oral Lowest published toxic dose (TDLo) in humans is 9 mg/kg/4W (intermittent).11
There is limited clinical experience in managing lenalidomide overdose. In single-dose studies, healthy subjects have been exposed to doses up to 400 mg. In clinical trials, the dose-limiting toxicity was neutropenia and thrombocytopenia. Toxicities associated with lenalidomide, some leading to fatality, include embryo-fetal toxicity, neutropenia, thrombocytopenia, venous (deep vein thrombosis and pulmonary embolism) and arterial thromboembolic events (myocardial infarction and stroke), serious adverse cardiovascular reactions, second primary malignancies, hepatotoxicity, severe cutaneous reactions, tumour lysis syndrome, tumour flare reaction, hypothyroidism, and hyperthyroidism.9
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Lenalidomide may decrease the excretion rate of Abacavir which could result in a higher serum level. Abatacept The risk or severity of adverse effects can be increased when Lenalidomide is combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Lenalidomide. Aceclofenac Aceclofenac may decrease the excretion rate of Lenalidomide which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Lenalidomide which could result in a higher serum level. - Food Interactions
- Take at the same time every day. Skip the missed dose if it has been more than 12 hours since your regular time.
- Take with or without food. High-fat meals decrease absorption, but not to a clinically significant extent.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Lenalidomide hydrochloride monohydrate Not Available Not Available Not applicable - International/Other Brands
- Ladevina / Lenangio
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eugia-lenalidomide Capsule 15 mg Oral Eugia Pharma Inc. Not applicable Not applicable Canada 
Eugia-lenalidomide Capsule 2.5 mg Oral Eugia Pharma Inc. Not applicable Not applicable Canada Eugia-lenalidomide Capsule 10 mg Oral Eugia Pharma Inc. Not applicable Not applicable Canada Eugia-lenalidomide Capsule 25 mg Oral Eugia Pharma Inc. Not applicable Not applicable Canada Eugia-lenalidomide Capsule 5 mg Oral Eugia Pharma Inc. Not applicable Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-lenalidomide Capsule 20 mg Oral Apotex Corporation 2021-09-01 Not applicable Canada Apo-lenalidomide Capsule 5 mg Oral Apotex Corporation 2021-09-01 Not applicable Canada Apo-lenalidomide Capsule 15 mg Oral Apotex Corporation 2021-09-01 Not applicable Canada Apo-lenalidomide Capsule 2.5 mg Oral Apotex Corporation 2021-09-01 Not applicable Canada Apo-lenalidomide Capsule 25 mg Oral Apotex Corporation 2021-09-01 Not applicable Canada
Categories
- ATC Codes
- L04AX04 — Lenalidomide
- Drug Categories
- Acids, Carbocyclic
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Drugs that are Mainly Renally Excreted
- Growth Inhibitors
- Growth Substances
- Heterocyclic Compounds, Fused-Ring
- Imides
- Immunologic Factors
- Immunosuppressive Agents
- Isoindoles
- Myelosuppressive Agents
- P-glycoprotein substrates
- Phthalic Acids
- Phthalimides
- Piperidines
- Piperidones
- Thalidomide Analog
- Tumor Necrosis Factor Blockers
- 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)
- Affected organisms
- Humans and other mammals
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
- 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. [Article]
- Anderson KC: Lenalidomide and thalidomide: mechanisms of action--similarities and differences. Semin Hematol. 2005 Oct;42(4 Suppl 4):S3-8. [Article]
- Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, Verma A: Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009 Aug 12;2:36. doi: 10.1186/1756-8722-2-36. [Article]
- Qiao SK, Guo XN, Ren JH, Ren HY: Efficacy and Safety of Lenalidomide in the Treatment of Multiple Myeloma: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Chin Med J (Engl). 2015 May 5;128(9):1215-22. doi: 10.4103/0366-6999.156134. [Article]
- Chen N, Wen L, Lau H, Surapaneni S, Kumar G: Pharmacokinetics, metabolism and excretion of [(14)C]-lenalidomide following oral administration in healthy male subjects. Cancer Chemother Pharmacol. 2012 Mar;69(3):789-97. doi: 10.1007/s00280-011-1760-3. Epub 2011 Oct 29. [Article]
- Fink EC, Ebert BL: The novel mechanism of lenalidomide activity. Blood. 2015 Nov 19;126(21):2366-9. doi: 10.1182/blood-2015-07-567958. Epub 2015 Oct 5. [Article]
- Galustian C, Dalgleish A: Lenalidomide: a novel anticancer drug with multiple modalities. Expert Opin Pharmacother. 2009 Jan;10(1):125-33. doi: 10.1517/14656560802627903. [Article]
- Kiaei M, Petri S, Kipiani K, Gardian G, Choi DK, Chen J, Calingasan NY, Schafer P, Muller GW, Stewart C, Hensley K, Beal MF: Thalidomide and lenalidomide extend survival in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci. 2006 Mar 1;26(9):2467-73. doi: 10.1523/JNEUROSCI.5253-05.2006. [Article]
- FDA Approved Products: Revlimid (Lenalidomide) oral capsules [Link]
- Celegene Corporation: Lenalidomide Safety Data Sheet [Link]
- Cayman Chemical: Lenalidomide Safety Data Sheet [Link]
- FDA Approved Products: REVLIMID (lenalidomide) capsules, for oral use 2022 [Link]
- External Links
- Human Metabolome Database
- HMDB0014623
- KEGG Drug
- D04687
- PubChem Compound
- 216326
- PubChem Substance
- 46505725
- ChemSpider
- 187515
- BindingDB
- 65454
- 342369
- ChEBI
- 63791
- ChEMBL
- CHEMBL848
- Therapeutic Targets Database
- DAP001255
- PharmGKB
- PA162363968
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lenalidomide
- FDA label
- Download (400 KB)
- MSDS
- Download (225 KB)
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Active Not Recruiting Not Available Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Completed Not Available Follicular Lymphoma ( FL) / Mantle Cell Lymphoma (MCL) / Myelodysplastic Syndrome 1 somestatus stop reason just information to hide Not Available Completed Not Available Multiple Myeloma (MM) 3 somestatus stop reason just information to hide Not Available Completed Not Available Myelodysplastic Syndrome 2 somestatus stop reason just information to hide Not Available Completed Not Available Relapsed/Refractory Multiple Myeloma (RRMM) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Celgene corp
- Celgene Corporation
- Packagers
- Celgene
- Norwich Pharmaceuticals Inc.
- Penn Pharmaceutical Services Ltd.
- Dosage Forms
Form Route Strength Capsule, coated Oral 10 mg Capsule Oral 2.5 MG Capsule Oral Capsule, coated Oral 15 mg Capsule, coated Oral 25 mg Capsule, coated Oral 5 mg Capsule Oral 15.000 mg Capsule Oral 7.5 mg Capsule Oral 10 mg/1 Capsule Oral 10.000 mg Capsule Oral 15 mg/1 Capsule Oral 2.5 mg/1 Capsule Oral 20 mg/1 Capsule Oral 20 mg Capsule Oral 25 mg/1 Capsule Oral 5 mg/1 Capsule Oral 10.0 mg Capsule Oral 15.0 mg Capsule Oral 25.0 mg Capsule Oral 5.0 mg Capsule Oral 10 mg Capsule Oral 15 mg Capsule Oral 25 mg Capsule Oral 5 mg - Prices
Unit description Cost Unit Revlimid 25 mg capsule 411.71USD capsule Revlimid 15 mg capsule 407.7USD capsule Revlimid 10 mg capsule 406.05USD capsule Revlimid 5 mg capsule 388.0USD 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 CA2477301 No 2009-09-01 2023-04-13 Canada CA2342974 No 2005-08-16 2014-02-24 Canada US6045501 No 2000-04-04 2018-08-28 US 
US6315720 No 2001-11-13 2020-10-23 US US6561976 No 2003-05-13 2018-08-28 US US6561977 No 2003-05-13 2020-10-23 US US6755784 No 2004-06-29 2020-10-23 US US6908432 No 2005-06-21 2018-08-28 US US8204763 No 2012-06-19 2018-08-28 US US8315886 No 2012-11-20 2020-10-23 US US8626531 No 2014-01-07 2020-10-23 US US8589188 No 2013-11-19 2018-08-28 US US7468363 No 2008-12-23 2023-10-07 US US6281230 No 2001-08-28 2016-07-24 US US8530498 No 2013-09-10 2023-05-15 US US6555554 No 2003-04-29 2016-07-24 US US7189740 No 2007-03-13 2023-04-11 US US7968569 No 2011-06-28 2023-10-07 US US8404717 No 2013-03-26 2023-04-11 US US8648095 No 2014-02-11 2023-05-15 US US8741929 No 2014-06-03 2028-03-08 US US9101622 No 2015-08-11 2023-05-15 US US9101621 No 2015-08-11 2023-05-15 US US9056120 No 2015-06-16 2023-04-11 US US5635517 No 1997-06-03 2019-10-04 US US7119106 No 2006-10-10 2016-07-24 US US7465800 No 2008-12-16 2027-04-27 US US7855217 No 2010-12-21 2024-11-24 US US8288415 No 2012-10-16 2016-07-24 US US9393238 No 2016-07-19 2023-05-15 US US8492406 No 2013-07-23 2023-10-07 US US9155730 No 2015-10-13 2023-05-15 US
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 logP -0.71 Chemaxon 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 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 68.3 m3·mol-1 Chemaxon Polarizability 25.51 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9958 Blood Brain Barrier + 0.9372 Caco-2 permeable - 0.5981 P-glycoprotein substrate Substrate 0.6845 P-glycoprotein inhibitor I Inhibitor 0.6012 P-glycoprotein inhibitor II Non-inhibitor 0.8927 Renal organic cation transporter Non-inhibitor 0.726 CYP450 2C9 substrate Non-substrate 0.8861 CYP450 2D6 substrate Non-substrate 0.7878 CYP450 3A4 substrate Substrate 0.5855 CYP450 1A2 substrate Non-inhibitor 0.8746 CYP450 2C9 inhibitor Non-inhibitor 0.8405 CYP450 2D6 inhibitor Non-inhibitor 0.8806 CYP450 2C19 inhibitor Non-inhibitor 0.78 CYP450 3A4 inhibitor Non-inhibitor 0.7469 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.843 Ames test Non AMES toxic 0.8268 Carcinogenicity Non-carcinogens 0.9068 Biodegradation Not ready biodegradable 0.9967 Rat acute toxicity 2.5145 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9803 hERG inhibition (predictor II) Non-inhibitor 0.5098
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 167.957836 predictedDarkChem Lite v0.1.0 [M-H]- 158.7324 predictedDeepCCS 1.0 (2019) [M+H]+ 168.307236 predictedDarkChem Lite v0.1.0 [M+H]+ 161.09041 predictedDeepCCS 1.0 (2019) [M+Na]+ 168.261836 predictedDarkChem Lite v0.1.0 [M+Na]+ 167.18356 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
- Specific Function
- cytokine activity
- Gene Name
- TNF
- Uniprot ID
- P01375
- Uniprot Name
- Tumor necrosis factor
- Molecular Weight
- 25644.15 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 or ILF2 (PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). Plays a negative role in TLR4 signaling by interacting with TRAF6 and ECSIT, leading to inhibition of ECSIT ubiquitination, an important step of the signaling (PubMed:31620128)
- Specific Function
- metal ion binding
- Gene Name
- CRBN
- Uniprot ID
- Q96SW2
- Uniprot Name
- Protein cereblon
- Molecular Weight
- 50545.375 Da
References
- 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]
- FDA Approved Products: Revlimid (Lenalidomide) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 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 (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity)
- Specific Function
- cytokine activity
- Gene Name
- TNFSF11
- Uniprot ID
- O14788
- Uniprot Name
- Tumor necrosis factor ligand superfamily member 11
- Molecular Weight
- 35477.81 Da
References
- 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. [Article]
- Melchert M, List A: The thalidomide saga. Int J Biochem Cell Biol. 2007;39(7-8):1489-99. Epub 2007 Jan 30. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Cadherins are calcium-dependent cell adhesion proteins (By similarity). They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types (PubMed:21269602). This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions (By similarity). It associates with alpha-catenin forming a link to the cytoskeleton (PubMed:10861224). Acts in concert with KRIT1 and PALS1 to establish and maintain correct endothelial cell polarity and vascular lumen (By similarity). These effects are mediated by recruitment and activation of the Par polarity complex and RAP1B (PubMed:20332120). Required for activation of PRKCZ and for the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction (PubMed:20332120)
- Specific Function
- beta-catenin binding
- Gene Name
- CDH5
- Uniprot ID
- P33151
- Uniprot Name
- Cadherin-5
- Molecular Weight
- 87527.715 Da
References
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Negative modulator
- General Function
- Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response (PubMed:11939906, PubMed:16373578, PubMed:19540099, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons (PubMed:16373578, PubMed:22942274, PubMed:26859324, PubMed:27226593, PubMed:7592599, PubMed:7947975, PubMed:9261177). Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins (PubMed:11939906, PubMed:19540099). In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids (PubMed:27642067). Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response (PubMed:22942274). Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols (PubMed:11034610, PubMed:11192938, PubMed:9048568, PubMed:9261177). Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation (PubMed:12391014). Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs) (PubMed:12391014). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2 (PubMed:21206090). In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection (PubMed:26236990). In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE) (PubMed:22068350, PubMed:26282205). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity)
- Specific Function
- enzyme binding
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- 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. [Article]
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- Chen N, Weiss D, Reyes J, Liu L, Kasserra C, Wang X, Zhou S, Kumar G, Weiss L, Palmisano M: No clinically significant drug interactions between lenalidomide and Pglycoprotein substrates and inhibitors: results from controlled phase I studies in healthy volunteers. Cancer Chemother Pharmacol. 2014 May;73(5):1031-9. doi: 10.1007/s00280-014-2438-4. [Article]
Drug created at June 13, 2005 13:24 / Updated at October 05, 2024 06:23