Explore a selection of our essential drug information below, or:
Identification
- Summary
Pomalidomide is a thalidomide analogue used in combination with dexamethasone to treat patients with multiple myeloma.
- Brand Names
- Imnovid, Pomalyst
- Generic Name
- Pomalidomide
- DrugBank Accession Number
- DB08910
- Background
Pomalidomide, an analogue of thalidomide, is an immunomodulatory antineoplastic agent. FDA approved on February 8, 2013.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Pomalidomide (DB08910)
- Weight
- Average: 273.2441
Monoisotopic: 273.074955855 - Chemical Formula
- C13H11N3O4
- Synonyms
- Pomalidomida
- Pomalidomide
- External IDs
- CC-4047
Pharmacology
- Indication
Pomalidomide is indicated for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and have demonstrated disease progression on or within 60 days of completion of the last therapy. It is also indicated for the treatment of Kaposi's sarcoma (KS) in AIDS patients who have failed highly active antiretroviral therapy (HAART) and for the treatment of KS in HIV-negative patients.4
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 Treatment of Kaposi's sarcoma •••••••••••• ••••• ••• •••••••• ••••••• Treatment of Kaposi's sarcoma •••••••••••• ••••• ••••••• •• •••••• •••••• •••••••••••••• ••••••• ••••••• ••••••• Used in combination to treat Multiple myeloma (mm) Regimen in combination with: Dexamethasone (DB01234) •••••••••••• ••••• ••••••• ••••••••••• •• •• •••••• •• •••• •• •••••••••• •• ••• •••• •••••••• •••••••• •• ••••• ••• ••••• ••••••••• ••••••••• •••••••••••• ••• • •••••••••• ••••••••• ••••••• Used in combination to treat Multiple myeloma (mm) Regimen in combination with: Isatuximab (DB14811), Dexamethasone (DB01234) •••••••••••• ••••• •••••••• •• ••••• ••• ••••• ••••••••• ••••••••• •••••••••••• ••• • •••••••••• ••••••••• •••••••••• ••••••••• •••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Pomalidomide is more potent than thalidomide (100-times) and lenalidomide (10-times).
- Mechanism of action
Promalidomide is an immunomodulatory agent with antineoplastic activity. It is shown to inhibit the proliferation and induce apoptosis of various tumour cells. Furthermore, promalidomide enhances T cell and natural killer (NK) cell-mediated immunity and inhibited the production of pro-inflammatory cytokines, like TNF-alpha or IL-6, by monocytes. The primary target of promalidomide is thought to be the protein cereblon. It binds to this target and inhibits ubiquitin ligase activity. It is also a transcriptional inhibitor of COX2.
Target Actions Organism AProtein cereblon inhibitorHumans ATumor necrosis factor inhibitorHumans AProstaglandin G/H synthase 2 inhibitorHumans - Absorption
Pomalidomide is generally well absorbed. The major circulating component is the parent compound. Tmax, single oral dose = 2 -3 hours. When 4 mg of promalidomide is given to patients with multiple myeloma, the steady-state pharmacokinetic parameters are as follows: AUC(T) = 400 ng.hr/mL; Cmax = 75 ng/mL. Promalidomide accumulates following multiple doses.
- Volume of distribution
Mean apparent volume of distribution (Vd/F), steady-state = 62 - 138 L
- Protein binding
12-44% protein bound. It is not concentration dependent.
- Metabolism
Promalidomide is hepatically metabolized by CYP1A2 and CYP3A4. The metabolites are 26-fold less active than the parent compound. Minor contributions from CYP2C19 and CYP2D6 have been observed in vitro.
- Route of elimination
When a single oral dose (2mg) is given to healthy subjects, 73% of the dose was eliminated in urine. 15% of the dose was eliminated in feces. 2% and 8% of the dose eliminated unchanged as pomalidomide in urine and feces, respectively.
- Half-life
Healthy subjects = 9.4 hours; Multiple myeloma patients = 7.5 hours.
- Clearance
Total body clearance = 7-10 L/hour
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Most common adverse reactions (≥30%) included fatigue and asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, upper-respiratory tract infections, back pain and pyrexia.
- 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 software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Pomalidomide is combined with 1,2-Benzodiazepine. Abacavir Abacavir may decrease the excretion rate of Pomalidomide which could result in a higher serum level. Abametapir The serum concentration of Pomalidomide can be increased when it is combined with Abametapir. Abatacept The metabolism of Pomalidomide can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Pomalidomide. - Food Interactions
- Take at the same time every day.
- Take with or without food. Administration of pomalidomide with food reduces the AUC and Cmax by 8% and 27%, respectively, and delays Tmax by two and a half hours.
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 Imnovid Capsule 1 mg Oral Bristol Myers Squibb Pharma Eeig 2020-12-21 Not applicable EU 
Imnovid Capsule 2 mg Oral Bristol Myers Squibb Pharma Eeig 2016-09-08 Not applicable EU Imnovid Capsule 3 mg Oral Bristol Myers Squibb Pharma Eeig 2020-12-21 Not applicable EU Imnovid Capsule 4 mg Oral Bristol Myers Squibb Pharma Eeig 2016-09-08 Not applicable EU Imnovid Capsule 1 mg Oral Bristol Myers Squibb Pharma Eeig 2016-09-08 Not applicable EU - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-pomalidomide Capsule 2 mg Oral Apotex Corporation 2023-02-28 Not applicable Canada 
Apo-pomalidomide Capsule 4 mg Oral Apotex Corporation 2023-02-28 Not applicable Canada Apo-pomalidomide Capsule 1 mg Oral Apotex Corporation 2023-02-28 Not applicable Canada Apo-pomalidomide Capsule 3 mg Oral Apotex Corporation 2023-02-28 Not applicable Canada Jamp Pomalidomide Capsule 1 mg Oral Jamp Pharma Corporation 2023-08-01 Not applicable Canada - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image IPOPRIN Pomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg) Capsule, coated Oral Msn Laboratories Private Limited 2019-12-13 2025-01-08 Colombia 
IPOPRIN Pomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg) Capsule, coated Oral Msn Laboratories Private Limited 2019-12-13 2025-01-08 Colombia IPOPRIN Pomalidomide (2 mg) + Pomalidomide (4 mg) + Pomalidomide (3 mg) Capsule, coated Oral Msn Laboratories Private Limited 2019-12-13 2025-01-08 Colombia
Categories
- ATC Codes
- L04AX06 — Pomalidomide
- Drug Categories
- Acids, Carbocyclic
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Cancer immunotherapy
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Growth Inhibitors
- Growth Substances
- Heterocyclic Compounds, Fused-Ring
- Imides
- Immunologic Factors
- Immunosuppressive Agents
- Immunotherapy
- Isoindoles
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- 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 phthalimides. These are aromatic heterocyclic compounds containing a 1,3-dioxoisoindoline moiety. They are imide derivatives of phthalic anhydrides.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Isoindoles and derivatives
- Sub Class
- Isoindolines
- Direct Parent
- Phthalimides
- Alternative Parents
- Alpha amino acids and derivatives / Isoindoles / Piperidinediones / Delta lactams / N-substituted carboxylic acid imides / Benzenoids / Vinylogous amides / N-unsubstituted carboxylic acid imides / Dicarboximides / Azacyclic compounds show 5 more
- Substituents
- Alpha-amino acid or derivatives / Amine / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative / Carboxylic acid imide / Carboxylic acid imide, n-substituted show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- dicarboximide, aromatic amine, piperidones, isoindoles (CHEBI:72690)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- D2UX06XLB5
- CAS number
- 19171-19-8
- InChI Key
- UVSMNLNDYGZFPF-UHFFFAOYSA-N
- InChI
- InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)
- IUPAC Name
- 4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
- SMILES
- NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O
References
- General References
- Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [Article]
- McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [Article]
- Terpos E, Kanellias N, Christoulas D, Kastritis E, Dimopoulos MA: Pomalidomide: a novel drug to treat relapsed and refractory multiple myeloma. Onco Targets Ther. 2013 May 10;6:531-8. doi: 10.2147/OTT.S34498. Print 2013. [Article]
- FDA Approved Drug Products: POMALYST (pomalidomide) capsules [Link]
- External Links
- KEGG Drug
- D08976
- PubChem Compound
- 134780
- PubChem Substance
- 175427148
- ChemSpider
- 118785
- BindingDB
- 65456
- 1369713
- ChEBI
- 72690
- ChEMBL
- CHEMBL43452
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Pomalidomide
- FDA label
- Download (292 KB)
- MSDS
- Download (479 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 Recruiting Not Available Multiple Myeloma (MM) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Relapsed/Refractory Multiple Myeloma (RRMM) 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Treatment Multiple Myeloma (MM) / Refractory Multiple Myeloma / Relapsed Multiple Myeloma 1 somestatus stop reason just information to hide 4 Recruiting Treatment Multiple Myeloma (MM) 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Multiple Myeloma (MM) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 3.000 mg Capsule, coated Oral Capsule Oral 1 mg/1 Capsule Oral 2 mg/1 Capsule Oral 3 mg/1 Capsule Oral 4 mg/1 Capsule, coated Oral 1 mg Capsule Oral 1 mg Capsule Oral 2 mg Capsule Oral 3 mg Capsule Oral 4 mg Capsule Oral Capsule, coated Oral 2 mg Capsule, coated Oral 3 mg Capsule, coated Oral 4 mg Capsule Oral 1.000 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region 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 US5635517 No 1997-06-03 2019-10-04 US US6316471 No 2001-11-13 2016-08-10 US US6476052 No 2002-11-05 2016-07-24 US US8198262 Yes 2012-06-12 2025-12-17 US US8673939 Yes 2014-03-18 2023-11-15 US US8735428 Yes 2014-05-27 2023-11-15 US US8828427 Yes 2014-09-09 2031-12-21 US US8158653 No 2012-04-17 2016-08-10 US US9993467 Yes 2018-06-12 2030-11-19 US US10555939 Yes 2020-02-11 2030-11-19 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 2.57 mg/mL ALOGPS logP 0.02 ALOGPS logP -0.16 Chemaxon logS -2 ALOGPS pKa (Strongest Acidic) 11.59 Chemaxon pKa (Strongest Basic) 1.56 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 109.57 Å2 Chemaxon Rotatable Bond Count 1 Chemaxon Refractivity 69.03 m3·mol-1 Chemaxon Polarizability 25.76 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9653 Blood Brain Barrier + 0.8304 Caco-2 permeable - 0.6419 P-glycoprotein substrate Substrate 0.5264 P-glycoprotein inhibitor I Non-inhibitor 0.5983 P-glycoprotein inhibitor II Non-inhibitor 0.9147 Renal organic cation transporter Non-inhibitor 0.847 CYP450 2C9 substrate Non-substrate 0.844 CYP450 2D6 substrate Non-substrate 0.8882 CYP450 3A4 substrate Substrate 0.5079 CYP450 1A2 substrate Non-inhibitor 0.8863 CYP450 2C9 inhibitor Non-inhibitor 0.8428 CYP450 2D6 inhibitor Non-inhibitor 0.9002 CYP450 2C19 inhibitor Non-inhibitor 0.8513 CYP450 3A4 inhibitor Non-inhibitor 0.7289 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8686 Ames test Non AMES toxic 0.7979 Carcinogenicity Non-carcinogens 0.9081 Biodegradation Not ready biodegradable 0.9858 Rat acute toxicity 2.5862 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9885 hERG inhibition (predictor II) Non-inhibitor 0.7765
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 162.72557 predictedDeepCCS 1.0 (2019) [M+H]+ 165.08357 predictedDeepCCS 1.0 (2019) [M+Na]+ 171.17674 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
- 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
- McCurdy AR, Lacy MQ: Pomalidomide and its clinical potential for relapsed or refractory multiple myeloma: an update for the hematologist. Ther Adv Hematol. 2013 Jun;4(3):211-6. doi: 10.1177/2040620713480155. [Article]
- Ito T, Ando H, Suzuki T, Ogura T, Hotta K, Imamura Y, Yamaguchi Y, Handa H: Identification of a primary target of thalidomide teratogenicity. Science. 2010 Mar 12;327(5971):1345-50. doi: 10.1126/science.1177319. [Article]
- Lopez-Girona A, Mendy D, Ito T, Miller K, Gandhi AK, Kang J, Karasawa S, Carmel G, Jackson P, Abbasian M, Mahmoudi A, Cathers B, Rychak E, Gaidarova S, Chen R, Schafer PH, Handa H, Daniel TO, Evans JF, Chopra R: Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide. Leukemia. 2012 Nov;26(11):2326-35. doi: 10.1038/leu.2012.119. Epub 2012 May 3. [Article]
- 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
- Gertz MA: Pomalidomide and myeloma meningitis. Leuk Lymphoma. 2013 Apr;54(4):681-2. doi: 10.3109/10428194.2012.723708. Epub 2013 Jan 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Ferguson GD, Jensen-Pergakes K, Wilkey C, Jhaveri U, Richard N, Verhelle D, De Parseval LM, Corral LG, Xie W, Morris CL, Brady H, Chan K: Immunomodulatory drug CC-4047 is a cell-type and stimulus-selective transcriptional inhibitor of cyclooxygenase 2. J Clin Immunol. 2007 Mar;27(2):210-20. Epub 2007 Feb 17. [Article]
Enzymes
- 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
- Li Y, Xu Y, Liu L, Wang X, Palmisano M, Zhou S: Population pharmacokinetics of pomalidomide. J Clin Pharmacol. 2015 May;55(5):563-72. doi: 10.1002/jcph.455. Epub 2015 Feb 4. [Article]
- Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]
- Pomalidomide FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]
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
References
- Kasserra C, Assaf M, Hoffmann M, Li Y, Liu L, Wang X, Kumar G, Palmisano M: Pomalidomide: evaluation of cytochrome P450 and transporter-mediated drug-drug interaction potential in vitro and in healthy subjects. J Clin Pharmacol. 2015 Feb;55(2):168-78. doi: 10.1002/jcph.384. Epub 2014 Sep 7. [Article]
Drug created at June 20, 2013 22:45 / Updated at April 23, 2024 11:38