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Identification
- Summary
Ponesimod is a sphingosine 1-phosphate receptor modulator indicated to treat relapsing multiple sclerosis.
- Brand Names
- Ponvory
- Generic Name
- Ponesimod
- DrugBank Accession Number
- DB12016
- Background
Ponesimod is a selective sphingosine 1-phosphate receptor 1 modulator indicated in the treatment of relapsing forms of multiple sclerosis in adults.1,3 Ponesimod was developed out of a need for a more selective modulator of sphingosine 1-phosphate receptor 1 than fingolimod.1 Fingolimod's activity at sphingosine 1-phosphate receptor 3 was suspected to be responsible for a portion of it's adverse effects, and so more selective modulators were developed.1
Ponesimod was granted FDA approval on 18 March 2021.3
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Ponesimod (DB12016)
- Weight
- Average: 460.97
Monoisotopic: 460.1223562 - Chemical Formula
- C23H25ClN2O4S
- Synonyms
- Ponesimod
- External IDs
- ACT 128800
- ACT-128800
- ACT128800
Pharmacology
- Indication
Ponesimod is indicated to treat adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.3
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 Active secondary progressive multiple sclerosis •••••••••••• ••••• •••••• Treatment of Relapsing multiple sclerosis (rms) •••••••••••• ••••• •••••• Treatment of Relapsing multiple sclerosis (rms) •••••••••••• ••••• •••••••••• •••••••• •••••••• ••••• •••••• Treatment of Relapsing remitting multiple sclerosis (rrms) •••••••••••• ••••• •••••• - 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
Ponesimod is a sphingosine 1-phosphate receptor 1 modulator indicated to treat adults with relapsing forms of multiple sclerosis.3 It has a long duration of action as it is given once daily.3 Patients should be counselled about the risk of infections, bradyarrhythmia, atrioventricular conduction delays, decreased respiratory function, liver injury, increased blood pressure, cutaneous malignancies, fetal harm, and macular edema.3
- Mechanism of action
The sphingosine 1-phosphate receptor 1 (S1P1R) is expressed on the surface of lymphocytes and detects sphingosine 1-phosphate (S1P) at nanomolar concentrations.2 S1P is a metabolite of the cell membrane component, sphingomyelin.2 As sphingomyelin degrades, lymphocytes respond to agonism of S1P1R by concentration gradients of S1P.2 Lymphocytes leave the lymphoid organs in response to higher concentrations of S1P in blood and lymph.2 Ponesimod modulates this response by stimulating and internalizing S1P1R on lymphocytes, effectively blinding them to concentration gradients of S1P, reducing the number of lymphocytes in blood.2,3 Ponesimod is roughly 650 times more selective for S1P1R than S1P.2
Target Actions Organism ASphingosine 1-phosphate receptor 1 agonistmodulatorregulatorHumans - Absorption
A 10mg oral dose of ponesimod is 84% bioavailable.3 Ponesimod reaches a Cmax of 109 ng/mL, with a Tmax of 4.0 hours, and an AUC of 3872 h*ng/mL.1
- Volume of distribution
The volume of distribution of ponesimod at steady state is 160 L.3
- Protein binding
Ponesimod is >99% protein bound in plasma.3 Though the proteins it binds to have not been identified in literature.3
- Metabolism
Ponesimod can be sulfated to the M5 metabolite, oxidized to an undefined M27 metabolite, reduced to the M6 metabolite, dealkylated to the M32 metabolite, or oxidized and hydrolyzed to the M13 metabolite.1,3 Ponesimod can also be oxidized by CYP2J2, CYP3A4, CYP3A5, CYP4F3A, and CYP4F12 to the M12 metabolite.1,3 The undefined M27 metabolite can be glucuronidated by UGT1A1 and UGT 2B7 to the M38, M39, and M40 metabolites.1,3 The M12 metabolite is either dealkylated to the M32 metabolite or oxidized and hydrolyzed to M13.1 M13 is dealkylated to M32, which is reduced and oxidized to M48.1
Hover over products below to view reaction partners
- Route of elimination
57.3-79.6% of a radiolabelled oral dose is recovered in the feces, with 16-26% as the unmetabolized parent compound and 22% as the M12 metabolite.1,3 10.3-18.4% of an oral dose is eliminated in the urine.1,3 0.6-1.9% of a radiolabelled dose was recovered as expired CO2.1
- Half-life
Ponesimod has an elimination half life of 33 hours.3
- Clearance
The clearance of ponesimod is 3.8 L/h.3
- 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
Patients experiencing an overdose may present with bradycardia, AV conduction block, and changes in blood pressure.3 Patients should be monitored for pulse rate and blood pressure, as well as ECGs.3 Treat patients with symptomatic and supportive measures, which may include atropine for bradycardia.3 dialysis is not expected to remove a significant amount of drug from blood.3
- 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 softwareAbametapir The serum concentration of Ponesimod can be increased when it is combined with Abametapir. Abatacept The metabolism of Ponesimod can be increased when combined with Abatacept. Acalabrutinib The metabolism of Ponesimod can be decreased when combined with Acalabrutinib. Acebutolol The risk or severity of bradycardia can be increased when Ponesimod is combined with Acebutolol. Acrivastine The risk or severity of bradycardia can be increased when Ponesimod is combined with Acrivastine. - Food Interactions
- Take with or without food. The absorption of ponesimod is not significantly affected by 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.- International/Other Brands
- Ponvory (Janssen)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ponvory Tablet, film coated 20 mg Oral Janssen Cilag International Nv 2022-05-04 Not applicable EU 
Ponvory Tablet, film coated 20 mg/1 Oral Janssen Pharmaceuticals, Inc 2021-03-18 2027-03-31 US 
Ponvory Tablet, film coated 20 mg Oral Janssen Cilag International Nv 2022-05-04 Not applicable EU Ponvory Tablet 20 mg Oral Janssen Pharmaceuticals 2021-11-01 Not applicable Canada 
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Ponvory Ponesimod (10 mg) + Ponesimod (2 mg) + Ponesimod (3 mg) + Ponesimod (4 mg) + Ponesimod (5 mg) + Ponesimod (6 mg) + Ponesimod (7 mg) + Ponesimod (8 mg) + Ponesimod (9 mg) Tablet Oral Janssen Pharmaceuticals 2021-11-01 Not applicable Canada Ponvory Ponesimod (2 mg/1) + Ponesimod (3 mg/1) + Ponesimod (4 mg/1) + Ponesimod (5 mg/1) + Ponesimod (6 mg/1) + Ponesimod (7 mg/1) + Ponesimod (8 mg/1) + Ponesimod (9 mg/1) + Ponesimod (10 mg/1) Kit; Tablet, film coated Oral Janssen Pharmaceuticals, Inc 2021-03-18 2027-03-31 US Ponvory Ponesimod (10 mg) + Ponesimod (2 mg) + Ponesimod (3 mg) + Ponesimod (4 mg) + Ponesimod (5 mg) + Ponesimod (6 mg) + Ponesimod (7 mg) + Ponesimod (8 mg) + Ponesimod (9 mg) Tablet Oral Janssen Pharmaceuticals 2021-11-01 Not applicable Canada Ponvory Ponesimod (10 mg) + Ponesimod (2 mg) + Ponesimod (3 mg) + Ponesimod (4 mg) + Ponesimod (5 mg) + Ponesimod (6 mg) + Ponesimod (7 mg) + Ponesimod (8 mg) + Ponesimod (9 mg) Tablet Oral Janssen Pharmaceuticals 2021-11-01 Not applicable Canada Ponvory Ponesimod (2 mg/1) + Ponesimod (3 mg/1) + Ponesimod (4 mg/1) + Ponesimod (5 mg/1) + Ponesimod (6 mg/1) + Ponesimod (7 mg/1) + Ponesimod (8 mg/1) + Ponesimod (9 mg/1) + Ponesimod (10 mg/1) Kit; Tablet, film coated Oral Janssen Pharmaceuticals, Inc 2021-03-18 2027-03-31 US
Categories
- ATC Codes
- L04AE04 — Ponesimod
- Drug Categories
- Antineoplastic and Immunomodulating Agents
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A5 Substrates
- Cytochrome P-450 Substrates
- Immunologic Factors
- Immunomodulatory Agents
- Immunosuppressive Agents
- Receptors, Lysosphingolipid, antagonists & inhibitors
- Selective Immunosuppressants
- Sphingosine 1 Phosphate Receptor Modulators
- Sphingosine 1-phosphate Receptor Modulator
- Sphingosine-1-phosphate (S1P) receptor modulators
- Sulfur Compounds
- UGT1A1 Substrates
- UGT2B7 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Phenol ethers
- Sub Class
- Not Available
- Direct Parent
- Phenol ethers
- Alternative Parents
- Phenoxy compounds / Toluenes / Alkyl aryl ethers / Chlorobenzenes / Aryl chlorides / Thiazolidines / Secondary alcohols / 1,2-diols / Isothioureas / Propargyl-type 1,3-dipolar organic compounds show 8 more
- Substituents
- 1,2-diol / Alcohol / Alkyl aryl ether / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Carbonyl group / Carboxylic acid derivative / Chlorobenzene show 21 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 5G7AKV2MKP
- CAS number
- 854107-55-4
- InChI Key
- LPAUOXUZGSBGDU-STDDISTJSA-N
- InChI
- InChI=1S/C23H25ClN2O4S/c1-3-10-25-23-26(19-7-5-4-6-15(19)2)22(29)21(31-23)12-16-8-9-20(18(24)11-16)30-14-17(28)13-27/h4-9,11-12,17,27-28H,3,10,13-14H2,1-2H3/b21-12-,25-23-/t17-/m1/s1
- IUPAC Name
- (2Z,5Z)-5-({3-chloro-4-[(2R)-2,3-dihydroxypropoxy]phenyl}methylidene)-3-(2-methylphenyl)-2-(propylimino)-1,3-thiazolidin-4-one
- SMILES
- CCC\N=C1/S\C(=C/C2=CC=C(OC[C@H](O)CO)C(Cl)=C2)C(=O)N1C1=CC=CC=C1C
References
- General References
- Reyes M, Hoch M, Brossard P, Wagner-Redeker W, Miraval T, Dingemanse J: Mass balance, pharmacokinetics and metabolism of the selective S1P1 receptor modulator ponesimod in humans. Xenobiotica. 2015 Feb;45(2):139-49. doi: 10.3109/00498254.2014.955832. Epub 2014 Sep 4. [Article]
- D'Ambrosio D, Freedman MS, Prinz J: Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases. Ther Adv Chronic Dis. 2016 Jan;7(1):18-33. doi: 10.1177/2040622315617354. [Article]
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- External Links
- PubChem Compound
- 11363176
- PubChem Substance
- 347828333
- ChemSpider
- 9538103
- BindingDB
- 50316768
- 2532300
- ChEMBL
- CHEMBL1096146
- ZINC
- ZINC000034509627
- Wikipedia
- Ponesimod
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 Completed Not Available Multiple Sclerosis 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Multiple Sclerosis 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Relapsing Remitting Multiple Sclerosis (RRMS) 1 somestatus stop reason just information to hide 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) / Multiple Sclerosis 1 somestatus stop reason just information to hide 3 Completed Treatment Multiple Sclerosis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Kit; tablet, film coated Oral Tablet Oral Tablet Oral 20 mg Tablet, film coated Oral 20 mg/1 Tablet, film coated Oral 20 MG - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8273779 No 2012-09-25 2025-12-17 US US9062014 No 2015-06-23 2032-05-06 US US9000018 No 2015-04-07 2024-11-16 US US10220023 No 2019-03-05 2035-12-10 US USRE43728 No 2012-10-09 2024-11-16 US US11951097 No 2022-10-10 2042-10-10 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Insoluble FDA Label - Predicted Properties
Property Value Source Water Solubility 0.00626 mg/mL ALOGPS logP 4.01 ALOGPS logP 4.49 Chemaxon logS -4.9 ALOGPS pKa (Strongest Acidic) 13.62 Chemaxon pKa (Strongest Basic) 0.91 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 82.36 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 125.69 m3·mol-1 Chemaxon Polarizability 49.67 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 splash10-01tc-1000900000-db64b7f426a5ec11bff6 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-059f-3003900000-10bd97f5dcc6a3d8d729 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-3004900000-d29aced208f0ef20ccb9 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-052o-9007300000-7cd595ec570fb5c9eebc Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000e-2169100000-933f5525227bb42b3a0a Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001m-5369000000-8caffb74b11a8a68732c 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]- 205.68571 predictedDeepCCS 1.0 (2019) [M+H]+ 208.08128 predictedDeepCCS 1.0 (2019) [M+Na]+ 214.50719 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AgonistModulatorRegulator
- General Function
- G-protein coupled receptor for the bioactive lysosphingolipid sphingosine 1-phosphate (S1P) that seems to be coupled to the G(i) subclass of heteromeric G proteins. Signaling leads to the activation of RAC1, SRC, PTK2/FAK1 and MAP kinases. Plays an important role in cell migration, probably via its role in the reorganization of the actin cytoskeleton and the formation of lamellipodia in response to stimuli that increase the activity of the sphingosine kinase SPHK1. Required for normal chemotaxis toward sphingosine 1-phosphate. Required for normal embryonic heart development and normal cardiac morphogenesis. Plays an important role in the regulation of sprouting angiogenesis and vascular maturation. Inhibits sprouting angiogenesis to prevent excessive sprouting during blood vessel development. Required for normal egress of mature T-cells from the thymus into the blood stream and into peripheral lymphoid organs. Plays a role in the migration of osteoclast precursor cells, the regulation of bone mineralization and bone homeostasis (By similarity). Plays a role in responses to oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine by pulmonary endothelial cells and in the protection against ventilator-induced lung injury
- Specific Function
- G protein-coupled receptor activity
- Gene Name
- S1PR1
- Uniprot ID
- P21453
- Uniprot Name
- Sphingosine 1-phosphate receptor 1
- Molecular Weight
- 42810.195 Da
References
- Reyes M, Brossard P, Chassard D, Hoch M, Dingemanse J: Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive. Eur J Clin Pharmacol. 2014 Mar;70(3):287-93. doi: 10.1007/s00228-013-1625-2. Epub 2013 Dec 22. [Article]
- D'Ambrosio D, Freedman MS, Prinz J: Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases. Ther Adv Chronic Dis. 2016 Jan;7(1):18-33. doi: 10.1177/2040622315617354. [Article]
- Olsson T, Boster A, Fernandez O, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M: Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1198-208. doi: 10.1136/jnnp-2013-307282. Epub 2014 Mar 21. [Article]
- D'Ambrosio D, Steinmann J, Brossard P, Dingemanse J: Differential effects of ponesimod, a selective S1P1 receptor modulator, on blood-circulating human T cell subpopulations. Immunopharmacol Immunotoxicol. 2015 Feb;37(1):103-9. doi: 10.3109/08923973.2014.993084. [Article]
- Guerard N, Zwingelstein C, Hoch M, Dingemanse J: Effect of Hepatic or Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of Ponesimod, a Selective S1P1 Receptor Modulator. Basic Clin Pharmacol Toxicol. 2016 May;118(5):356-68. doi: 10.1111/bcpt.12516. Epub 2015 Dec 10. [Article]
- Reyes M, Hoch M, Brossard P, Dingemanse J: Effects of ethnicity and sex on the pharmacokinetics and pharmacodynamics of the selective sphingosine-1-phosphate receptor 1 modulator ponesimod: a clinical study in Japanese and Caucasian subjects. Pharmacology. 2014;94(5-6):223-9. doi: 10.1159/000368837. Epub 2014 Nov 14. [Article]
- Lott D, Krause A, Seemayer CA, Strasser DS, Dingemanse J, Lehr T: Modeling the Effect of the Selective S1P1 Receptor Modulator Ponesimod on Subsets of Blood Lymphocytes. Pharm Res. 2017 Mar;34(3):599-609. doi: 10.1007/s11095-016-2087-x. Epub 2016 Dec 27. [Article]
- Juif PE, Hoch M, Vaclavkova A, Krause A, Bush J, Dingemanse J: Mitigation of Initial Cardiodynamic Effects of the S1P1 Receptor Modulator Ponesimod Using a Novel Up-Titration Regimen. J Clin Pharmacol. 2017 Mar;57(3):401-410. doi: 10.1002/jcph.820. Epub 2016 Sep 30. [Article]
- Fauzyah Y, Ono C, Torii S, Anzai I, Suzuki R, Izumi T, Morioka Y, Maeda Y, Okamoto T, Fukuhara T, Matsuura Y: Ponesimod suppresses hepatitis B virus infection by inhibiting endosome maturation. Antiviral Res. 2021 Feb;186:104999. doi: 10.1016/j.antiviral.2020.104999. Epub 2020 Dec 18. [Article]
- Boehler M, Juif PE, Hoch M, Dingemanse J: Absolute Bioavailability of Ponesimod, a Selective S1P1 Receptor Modulator, in Healthy Male Subjects. Eur J Drug Metab Pharmacokinet. 2017 Feb;42(1):129-134. doi: 10.1007/s13318-016-0325-6. [Article]
- Pouzol L, Piali L, Bernard CC, Martinic MM, Steiner B, Clozel M: Therapeutic Potential of Ponesimod Alone and in Combination with Dimethyl Fumarate in Experimental Models of Multiple Sclerosis. Innov Clin Neurosci. 2019 Mar 1;16(3-4):22-30. [Article]
- Hoch M, D'Ambrosio D, Wilbraham D, Brossard P, Dingemanse J: Clinical pharmacology of ponesimod, a selective S1P(1) receptor modulator, after uptitration to supratherapeutic doses in healthy subjects. Eur J Pharm Sci. 2014 Oct 15;63:147-53. doi: 10.1016/j.ejps.2014.07.005. Epub 2014 Jul 19. [Article]
- Juif PE, Hoch M, D'Ambrosio D, Dingemanse J: Biocomparison of Three Formulations of the S1P1 Receptor Modulator Ponesimod in Healthy Subjects. Drugs R D. 2015 Jun;15(2):203-10. doi: 10.1007/s40268-015-0095-7. [Article]
- Bell M, Foley D, Naylor C, Robinson C, Riley J, Epemolu O, Scullion P, Shishikura Y, Katz E, McLean WHI, Wyatt P, Read KD, Woodland A: Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1. Bioorg Med Chem Lett. 2018 Oct 15;28(19):3255-3259. doi: 10.1016/j.bmcl.2018.07.044. Epub 2018 Jul 30. [Article]
- Janes K, Little JW, Li C, Bryant L, Chen C, Chen Z, Kamocki K, Doyle T, Snider A, Esposito E, Cuzzocrea S, Bieberich E, Obeid L, Petrache I, Nicol G, Neumann WL, Salvemini D: The development and maintenance of paclitaxel-induced neuropathic pain require activation of the sphingosine 1-phosphate receptor subtype 1. J Biol Chem. 2014 Jul 25;289(30):21082-97. doi: 10.1074/jbc.M114.569574. [Article]
- Gatfield J, Monnier L, Studer R, Bolli MH, Steiner B, Nayler O: Sphingosine-1-phosphate (S1P) displays sustained S1P1 receptor agonism and signaling through S1P lyase-dependent receptor recycling. Cell Signal. 2014 Jul;26(7):1576-88. doi: 10.1016/j.cellsig.2014.03.029. Epub 2014 Apr 2. [Article]
- Borodzicz S, Rudnicka L, Mirowska-Guzel D, Cudnoch-Jedrzejewska A: The role of epidermal sphingolipids in dermatologic diseases. Lipids Health Dis. 2016 Jan 19;15:13. doi: 10.1186/s12944-016-0178-7. [Article]
- Vaclavkova A, Chimenti S, Arenberger P, Hollo P, Sator PG, Burcklen M, Stefani M, D'Ambrosio D: Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Dec 6;384(9959):2036-45. doi: 10.1016/S0140-6736(14)60803-5. Epub 2014 Aug 10. [Article]
- 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]
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) in the cardiovascular system (PubMed:19965576, PubMed:8631948). 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:19965576, PubMed:8631948). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:8631948). Converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE), likely playing a major role in the epoxidation of endogenous cardiac arachidonic acid pools (PubMed:8631948). In endothelial cells, participates in eicosanoids metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent (PubMed:19737933). Catalyzes the monooxygenation of a various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A and nabumetone (PubMed:19923256). Catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole (PubMed:23959307). Catalyzes the sulfoxidation of fenbedazole (PubMed:19923256)
- Specific Function
- arachidonic acid 11,12-epoxygenase activity
- Gene Name
- CYP2J2
- Uniprot ID
- P51589
- Uniprot Name
- Cytochrome P450 2J2
- Molecular Weight
- 57610.165 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- 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
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). 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:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion 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 all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228)
- Specific Function
- aromatase activity
- Gene Name
- CYP3A5
- Uniprot ID
- P20815
- Uniprot Name
- Cytochrome P450 3A5
- Molecular Weight
- 57108.065 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- 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 and their oxygenated derivatives (oxylipins) (PubMed:11461919, PubMed:15145985, PubMed:16547005, PubMed:16820285, PubMed:18065749, PubMed:18182499, PubMed:18577768, PubMed:8486631, PubMed:9675028). 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 (CPR; NADPH-ferrihemoprotein reductase) (PubMed:9675028). May play a role in inactivation of pro-inflammatory and anti-inflammatory oxylipins during the resolution of inflammation (PubMed:11461919, PubMed:15145985, PubMed:15364545, PubMed:16547005, PubMed:16820285, PubMed:18065749, PubMed:18182499, PubMed:18577768, PubMed:8486631, PubMed:9675028)
- Specific Function
- 20-aldehyde-leukotriene B4 20-monooxygenase activity
- Gene Name
- CYP4F3
- Uniprot ID
- Q08477
- Uniprot Name
- Cytochrome P450 4F3
- Molecular Weight
- 59846.085 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endogenous polyunsaturated fatty acids (PUFAs). 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 (CPR; NADPH-ferrihemoprotein reductase). Catalyzes the hydroxylation of carbon hydrogen bonds, with preference for omega-2 position. Metabolizes (5Z,8Z,11Z,14Z)-eicosatetraenoic acid (arachidonate) toward 18-hydroxy arachidonate (PubMed:11162607). Catalyzes the epoxidation of double bonds of PUFAs such as docosapentaenoic and docosahexaenoic acids (PubMed:16112640). Has low omega-hydroxylase activity toward leukotriene B4 and arachidonate (PubMed:11162645). Involved in the metabolism of xenobiotics. Catalyzes the hydroxylation of the antihistamine drug ebastine (PubMed:11162645)
- Specific Function
- alkane 1-monooxygenase activity
- Gene Name
- CYP4F12
- Uniprot ID
- Q9HCS2
- Uniprot Name
- Cytochrome P450 4F12
- Molecular Weight
- 60308.195 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:18004206, PubMed:18004212, PubMed:18719240, PubMed:19830808, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004206, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol, estrone and estriol (PubMed:15472229, PubMed:18719240, PubMed:23288867). Involved in the glucuronidation of bilirubin, a degradation product occurring in the normal catabolic pathway that breaks down heme in vertebrates (PubMed:17187418, PubMed:18004206, PubMed:19830808, PubMed:24525562). Also catalyzes the glucuronidation the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:18004212, PubMed:20610558)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1A1
- Molecular Weight
- 59590.91 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10702251, PubMed:15470161, PubMed:15472229, PubMed:17442341, PubMed:18674515, PubMed:18719240, PubMed:19022937, PubMed:23288867, PubMed:23756265, PubMed:26220143). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:15470161, PubMed:18674515, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (epitestosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:15472229, PubMed:17442341, PubMed:18719240, PubMed:19022937, PubMed:2159463, PubMed:23288867, PubMed:26220143). Also regulates the levels of retinoic acid, a major metabolite of vitamin A involved in apoptosis, cellular growth and differentiation, and embryonic development (PubMed:10702251). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist losartan, caderastan and zolarsatan, drugs which can inhibit the effect of angiotensin II (PubMed:18674515). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161)
- Specific Function
- glucuronosyltransferase activity
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60720.15 Da
References
- FDA Approved Drug Products: Ponvory (Ponesimod) Oral Tablet [Link]
Drug created at October 20, 2016 21:11 / Updated at April 23, 2024 11:38