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Identification
- Summary
Apremilast is a non-steroidal medication used for the treatment of inflammatory conditions such as psoriasis and psoriatic arthritis.
- Brand Names
- Otezla
- Generic Name
- Apremilast
- DrugBank Accession Number
- DB05676
- Background
Apremilast, also known as Otezla, is a phosphodiesterase 4 (PDE4) inhibitor used to treat various types of symptoms resulting from certain inflammatory autoimmune diseases. It belongs to the same drug class as Roflumilast and Crisaborole.11,12 Initially approved in 2014, it is marketed by Celgene.14 In July 2019, apremilast was granted a new FDA approval for the treatment of oral ulcers associated with Behcet's disease, an autoimmune condition that causes recurrent skin, blood vessel, and central nervous system inflammation.4
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Apremilast (DB05676)
- Weight
- Average: 460.5
Monoisotopic: 460.130422295 - Chemical Formula
- C22H24N2O7S
- Synonyms
- Aprémilast
- Apremilast
- Apremilastum
- N-{2-[(1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide
- External IDs
- CC 10004
- CC-10004
- CC10004
Pharmacology
- Indication
Apremilast is indicated for the treatment of adults with active psoriatic arthritis and adults with oral ulcers associated with Behcet's Disease. In addition, apremilast is indicated for the treatment of plaque psoriasis, of any severity, in adult patients who are candidates for phototherapy or systemic therapy.14
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Psoriasis vulgaris (plaque psoriasis) •••••••••••• ••••• ••••••••• ••• •••••••• ••••••• Management of Psoriasis vulgaris (plaque psoriasis) •••••••••••• ••••• •••••••••• ••• •••••••••••• Treatment of Psoriasis vulgaris (plaque psoriasis) •••••••••••• ••••• •••••••••• ••• •••••••••••• •••••• Treatment of Psoriasis vulgaris (plaque psoriasis) •••••••••••• ••••• •••••••••• ••• •••••••• ••••••• ••• ••••••••• •••••• Management of Active psoriatic arthritis •••••••••••• ••••• - Contraindications & Blackbox Warnings
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Apremilast reduces but does not completely inhibit various inflammatory cytokines such as IL-1α, IL-6, IL-8, IL-10 MCP-1, MIP-1β, MMP-3, and TNF-α, relieving the symptoms of psoriasis and Behcet's disease, which are caused by an increase in these inflammatory mediators.6,13 This drug has also been proven to be effective in relieving the pain associated with oral ulcers in Behcet's disease.11
Apremilast may cause unwanted weight loss and worsen depression, leading to suicidal thoughts or actions. It is advisable to monitor for symptoms of depression and seek medical attention if they occur, especially in patients with pre-existing depression. The need for apremilast should be carefully assessed along with the risk of worsening depression and suicide. If weight loss occurs, the degree of weight loss should be evaluated, and consideration should be made for the possible discontinuation of apremilast.14
- Mechanism of action
The full mechanism of action of this drug is not fully established, however, it is known that apremilast is an inhibitor of phosphodiesterase 4 (PDE4), which mediates the activity of cyclic adenosine monophosphate (cAMP), a second messenger.5 The inhibition of PDE4 by apremilast leads to increased intracellular cAMP levels.14 An increase in cAMP results in the suppression of inflammation by decreasing the expression of TNF-α, IL-17, IL-23, and other inflammatory mediators. The above inflammatory mediators have been implicated in various psoriatic conditions as well as Behcet's disease, leading to their undesirable inflammatory symptoms such as mouth ulcers, skin lesions, and arthritis.6,13,14 Apremilast administration leads to a cascade which eventually decreases the levels of the above mediators, relieving inflammatory symptoms.
Target Actions Organism APhosphodiesterase isozyme 4 inhibitorHumans ACyclin-dependent kinase 4 inhibitorHumans ACyclin-dependent kinase 6 inhibitorHumans - Absorption
An oral dose of apremilast is well-absorbed and the absolute bioavailability is approximately 73%. Tmax is approximately 2.5 hours14 and Cmax has been reported to be approximately 584 ng/mL in one pharmacokinetic study.8 Food intake does not appear to affect apremilast absorption.14
- Volume of distribution
The average apparent volume of distribution (Vd) is about 87 L, suggesting that apremilast is distributed in the extravascular compartment.13
- Protein binding
The plasma protein binding of apremilast is about 68%.13
- Metabolism
Apremilast is heavily metabolized by various pathways, which include oxidation, hydrolysis, in addition to conjugation. About 23 metabolites are produced from its metabolism.3 The CYP3A4 primarily mediates the oxidative metabolism of this drug, with smaller contributions from CYP1A2 and CYP2A6 enzymes.13 The main metabolite of apremilast, M12, is an inactive glucuronide conjugate form of the O-demethylated drug.13 Some other major metabolites, M14 and M16, are significantly less active in the inhibition of PDE4 and inflammatory mediators than their parent drug, apremilast. After an oral dose, unchanged apremilast (45%) and the inactive metabolite, O-desmethyl apremilast glucuronide (39%) are found in the plasma. 10 Minor metabolites M7 and M17 are active, but are only present in about 2% or less of apremilast concentrations, and likely not significant contributors to the actions of apremilast.10
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- Route of elimination
Only 3% and 7% of an apremilast dose are detected in the urine and feces as unchanged drug, respectively, indicating extensive metabolism and high absorption.13
- Half-life
The average elimination half-life of this drug ranges from 6-9 hours.7,14
- Clearance
In healthy patients, the plasma clearance of apremilast is about 10 L/hour.13
- Adverse Effects
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The oral LD50 in mice was greater than 2000 mg/kg in mice. In rats, oral LD50 was 2000 mg/kg males and 300 mg/kg in females.16
Overdose information
In healthy subjects receiving a maximum dose of 100 mg (given as 50 mg twice daily) for about 5 days, no significant toxicity was observed. In cases of an overdose, supportive and symptomatic treatment should be administered. Contact the local poison control center for the most recent overdose management for apremilast.15
- 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 Abacavir may decrease the excretion rate of Apremilast which could result in a higher serum level. Abametapir The serum concentration of Apremilast can be increased when it is combined with Abametapir. Abatacept The therapeutic efficacy of Apremilast can be decreased when used in combination with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Apremilast. Abiraterone The serum concentration of Apremilast can be increased when it is combined with Abiraterone. - Food Interactions
- Avoid St. John's Wort. Apremilast is a CYP3A substrate; therefore, co-administration with St. John's wort, a CYP3A inducer, may reduce the serum level of apremilast.
- Take with or without food.
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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apremilast Accord Tablet, film coated 30 mg Oral Accord Healthcare, S.L.U. 2024-07-10 Not applicable EU 
Apremilast Accord Tablet, film coated 30 mg Oral Accord Healthcare, S.L.U. 2024-07-10 Not applicable EU Apremilast Accord Tablet, film coated 30 mg Oral Accord Healthcare, S.L.U. 2024-07-10 Not applicable EU Gln-apremilast Tablet 30 mg Oral Glenmark Pharmaceuticals Inc., USA 2022-11-14 Not applicable Canada 
Otezla Tablet, film coated 30 mg Oral Amgen Europe B.V. 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-apremilast Tablet 30 mg Oral Apotex Corporation 2023-09-28 Not applicable Canada Apo-apremilast Tablets Tablet 30 mg Oral Apotex Corporation Not applicable Not applicable Canada Apremilast Tablet, film coated 30 mg/1 Oral Camber Pharmaceuticals, Inc. 2023-07-26 Not applicable US 
Apremilast Tablet, film coated 30 mg/1 Oral Amneal Pharmaceuticals NY LLC 2021-07-05 Not applicable US Auro-apremilast Tablet 30 mg Oral Auro Pharma Inc 2022-12-07 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Apo-apremilast Apremilast (10 mg) + Apremilast (20 mg) + Apremilast (30 mg) Tablet Oral Apotex Corporation Not applicable Not applicable Canada Apo-apremilast Apremilast (10 mg) + Apremilast (20 mg) + Apremilast (30 mg) Tablet Oral Apotex Corporation Not applicable Not applicable Canada Apo-apremilast Apremilast (10 mg) + Apremilast (20 mg) + Apremilast (30 mg) Tablet Oral Apotex Corporation Not applicable Not applicable Canada Apo-apremilast Tablets Apremilast (10 mg) + Apremilast (20 mg) + Apremilast (30 mg) Tablet Oral Apotex Corporation Not applicable Not applicable Canada Apo-apremilast Tablets Apremilast (10 mg) + Apremilast (20 mg) + Apremilast (30 mg) Tablet Oral Apotex Corporation Not applicable Not applicable Canada
Categories
- ATC Codes
- L04AA32 — Apremilast
- Drug Categories
- Agents reducing cytokine levels
- Anti-Inflammatory Agents
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Disease-modifying Antirheumatic Agents
- Drugs that are Mainly Renally Excreted
- Enzyme Inhibitors
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Immunotherapy
- Isoindoles
- P-glycoprotein substrates
- Phosphodiesterase 4 Inhibitors
- Phosphodiesterase Inhibitors
- Phthalimides
- Selective Immunosuppressants
- 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
- Isoindoles / N-acetylarylamines / Anisoles / Methoxybenzenes / Phenoxy compounds / Alkyl aryl ethers / N-substituted carboxylic acid imides / Sulfones / Vinylogous amides / Acetamides show 6 more
- Substituents
- Acetamide / Alkyl aryl ether / Anisole / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Carboxylic acid imide show 22 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- aromatic ether, sulfone, phthalimides, N-acetylarylamine (CHEBI:78540)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- UP7QBP99PN
- CAS number
- 608141-41-9
- InChI Key
- IMOZEMNVLZVGJZ-QGZVFWFLSA-N
- InChI
- InChI=1S/C22H24N2O7S/c1-5-31-19-11-14(9-10-18(19)30-3)17(12-32(4,28)29)24-21(26)15-7-6-8-16(23-13(2)25)20(15)22(24)27/h6-11,17H,5,12H2,1-4H3,(H,23,25)/t17-/m1/s1
- IUPAC Name
- N-{2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide
- SMILES
- CCOC1=CC(=CC=C1OC)[C@@H](CS(C)(=O)=O)N1C(=O)C2=CC=CC(NC(C)=O)=C2C1=O
References
- General References
- Molostvov G, Morris A, Rose P, Basu S, Muller G: The effects of selective cytokine inhibitory drugs (CC-10004 and CC-1088) on VEGF and IL-6 expression and apoptosis in myeloma and endothelial cell co-cultures. Br J Haematol. 2004 Feb;124(3):366-75. [Article]
- Abdulrahim H, Thistleton S, Adebajo AO, Shaw T, Edwards C, Wells A: Apremilast: a PDE4 inhibitor for the treatment of psoriatic arthritis. Expert Opin Pharmacother. 2015 May;16(7):1099-108. doi: 10.1517/14656566.2015.1034107. Epub 2015 Apr 11. [Article]
- Hoffmann M, Kumar G, Schafer P, Cedzik D, Capone L, Fong KL, Gu Z, Heller D, Feng H, Surapaneni S, Laskin O, Wu A: Disposition, metabolism and mass balance of [(14)C]apremilast following oral administration. Xenobiotica. 2011 Dec;41(12):1063-75. doi: 10.3109/00498254.2011.604745. Epub 2011 Aug 23. [Article]
- Suzuki Kurokawa M, Suzuki N: Behcet's disease. Clin Exp Med. 2004 Sep;4(1):10-20. [Article]
- Fertig BA, Baillie GS: PDE4-Mediated cAMP Signalling. J Cardiovasc Dev Dis. 2018 Jan 31;5(1). pii: jcdd5010008. doi: 10.3390/jcdd5010008. [Article]
- Tong B, Liu X, Xiao J, Su G: Immunopathogenesis of Behcet's Disease. Front Immunol. 2019 Mar 29;10:665. doi: 10.3389/fimmu.2019.00665. eCollection 2019. [Article]
- Young M, Roebuck HL: Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment option for nurse practitioners treating patients with psoriatic disease. J Am Assoc Nurse Pract. 2016 Dec;28(12):683-695. doi: 10.1002/2327-6924.12428. Epub 2016 Nov 21. [Article]
- Liu Y, Zhou S, Nissel J, Wu A, Lau H, Palmisano M: The pharmacokinetic effect of coadministration of apremilast and methotrexate in individuals with rheumatoid arthritis and psoriatic arthritis. Clin Pharmacol Drug Dev. 2014 Nov;3(6):456-465. doi: 10.1002/cpdd.109. Epub 2014 May 8. [Article]
- Zerilli T, Ocheretyaner E: Apremilast (Otezla): A New Oral Treatment for Adults With Psoriasis and Psoriatic Arthritis. P T. 2015 Aug;40(8):495-500. [Article]
- Cada DJ, Ingram K, Baker DE: Apremilast. Hosp Pharm. 2014 Sep;49(8):752-62. doi: 10.1310/hpj4908-752. [Article]
- Afra TP, Razmi TM, Dogra S: Apremilast in Psoriasis and Beyond: Big Hopes on a Small Molecule. Indian Dermatol Online J. 2019 Jan-Feb;10(1):1-12. doi: 10.4103/idoj.IDOJ_437_18. [Article]
- FDA approvals, Otezla [Link]
- Otezla product information [Link]
- FDA Approved Drug Products: Otezla (apremilast) tablets for oral use [Link]
- Medsafe NZ [Link]
- EMA label, Otezla [Link]
- External Links
- KEGG Drug
- D08860
- PubChem Compound
- 11561674
- PubChem Substance
- 310264858
- ChemSpider
- 9736448
- BindingDB
- 50248919
- 1492727
- ChEBI
- 78540
- ChEMBL
- CHEMBL514800
- ZINC
- ZINC000030691736
- PDBe Ligand
- A9L
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Apremilast
- PDB Entries
- 7cbq
- MSDS
- Download (104 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 Psoriasis / Psoriatic Arthritis 1 somestatus stop reason just information to hide Not Available Completed Not Available Psoriasis 3 somestatus stop reason just information to hide Not Available Completed Not Available Psoriasis Nail 1 somestatus stop reason just information to hide Not Available Completed Not Available Psoriasis Vulgaris (Plaque Psoriasis) 1 somestatus stop reason just information to hide Not Available Completed Not Available Psoriasis / Psoriatic Arthritis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 10 mg Tablet Oral 20 mg Kit Oral Kit; tablet, film coated Oral Tablet Oral Tablet Oral 30 mg Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 30 mg/1 Tablet, film coated Oral 30.0 mg/1 Tablet, coated Oral Tablet, coated Oral 30 mg Tablet, film coated Oral 10 mg Tablet, film coated Oral 20 mg Tablet, film coated Oral 30 mg Tablet, film coated Oral - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8802717 No 2014-08-12 2023-03-19 US US6962940 No 2005-11-08 2023-03-19 US US6020358 No 2000-02-01 2018-10-30 US US7208516 No 2007-04-24 2023-03-19 US US7659302 No 2010-02-09 2023-03-19 US US8455536 No 2013-06-04 2023-03-19 US US9018243 No 2015-04-28 2023-03-19 US US7427638 Yes 2008-09-23 2028-08-16 US US7893101 No 2011-02-22 2023-12-09 US US9872854 Yes 2018-01-23 2034-11-29 US US9724330 No 2017-08-08 2023-03-19 US US10092541 Yes 2018-10-09 2034-11-29 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156.1 http://www.guildlink.com.au/gc/ws/celgene/pi.cfm?product=cjpaprem boiling point (°C) 741.3±60.0 http://www.chemspider.com/Chemical-Structure.9736448.html pKa 12.58 https://pubchem.ncbi.nlm.nih.gov/compound/Apremilast#section=Solubility - Predicted Properties
Property Value Source Water Solubility 0.0341 mg/mL ALOGPS logP 1.86 ALOGPS logP 1.31 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 12.98 Chemaxon pKa (Strongest Basic) -4.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 119.08 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 119.1 m3·mol-1 Chemaxon Polarizability 46.71 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 Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-0000900000-4fa09deea89e17357555 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-066r-1000900000-cc0757be6053d8d34230 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-02t9-0365900000-a7a9ec2eaa036bfc9807 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0cgi-1001900000-34e03e07eceb3110e43a Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udr-0329300000-fd8a063994b2e7a1c06f Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-000i-2926500000-9f9145b4948f3748e11b Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 199.93428 predictedDeepCCS 1.0 (2019) [M+H]+ 202.32982 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.24236 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Not Available
- Specific Function
- 3',5'-cyclic-AMP phosphodiesterase activity
- Gene Name
- PDE4
- Uniprot ID
- Q86V67
- Uniprot Name
- Phosphodiesterase isozyme 4
- Molecular Weight
- 11946.535 Da
References
- Baumer W, Hoppmann J, Rundfeldt C, Kietzmann M: Highly selective phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and psoriasis. Inflamm Allergy Drug Targets. 2007 Mar;6(1):17-26. [Article]
- Abdulrahim H, Thistleton S, Adebajo AO, Shaw T, Edwards C, Wells A: Apremilast: a PDE4 inhibitor for the treatment of psoriatic arthritis. Expert Opin Pharmacother. 2015 May;16(7):1099-108. doi: 10.1517/14656566.2015.1034107. Epub 2015 Apr 11. [Article]
- Afra TP, Razmi TM, Dogra S: Apremilast in Psoriasis and Beyond: Big Hopes on a Small Molecule. Indian Dermatol Online J. 2019 Jan-Feb;10(1):1-12. doi: 10.4103/idoj.IDOJ_437_18. [Article]
- FDA Approved Drug Products: Otezla (apremilast) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex
- Specific Function
- ATP binding
- Gene Name
- CDK4
- Uniprot ID
- P11802
- Uniprot Name
- Cyclin-dependent kinase 4
- Molecular Weight
- 33729.55 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
- Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and negatively regulates cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663)
- Specific Function
- ATP binding
- Gene Name
- CDK6
- Uniprot ID
- Q00534
- Uniprot Name
- Cyclin-dependent kinase 6
- Molecular Weight
- 36938.025 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]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Hoffmann M, Kumar G, Schafer P, Cedzik D, Capone L, Fong KL, Gu Z, Heller D, Feng H, Surapaneni S, Laskin O, Wu A: Disposition, metabolism and mass balance of [(14)C]apremilast following oral administration. Xenobiotica. 2011 Dec;41(12):1063-75. doi: 10.3109/00498254.2011.604745. Epub 2011 Aug 23. [Article]
- Zerilli T, Ocheretyaner E: Apremilast (Otezla): A New Oral Treatment for Adults With Psoriasis and Psoriatic Arthritis. P T. 2015 Aug;40(8):495-500. [Article]
- Young M, Roebuck HL: Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor: A novel treatment option for nurse practitioners treating patients with psoriatic disease. J Am Assoc Nurse Pract. 2016 Dec;28(12):683-695. doi: 10.1002/2327-6924.12428. Epub 2016 Nov 21. [Article]
- FDA Approved Drug Products: Otezla (apremilast) tablets for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56517.005 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
Drug created at November 18, 2007 18:26 / Updated at October 11, 2024 22:17