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Identification
- Summary
Tecovirimat is an antiviral medication used to treat smallpox, monkeypox, and cowpox.
- Brand Names
- Tpoxx
- Generic Name
- Tecovirimat
- DrugBank Accession Number
- DB12020
- Background
The World Health Organization declared smallpox, a contagious and sometimes fatal infectious disease, eradicated in 1980. However, there have been longstanding concerns that smallpox may be used as a bioweapon.2,5 Tecovirimat is an antiviral drug that was identified via a high-throughput screen in 2002.2 It is effective against all orthopoxviruses, including vaccinia, cowpox, ectromelia, rabbitpox, monkeypox, and Variola (smallpox) virus.1,4
Tecovirimat was approved by the FDA in July 2018 as the first drug ever approved to treat smallpox.6,5 Tecovirimat was later approved by Health Canada in December 2021,7 followed by the approval from the European Commission in January 2022.9 Other than smallpox, tecovirimat is also indicated to treat complications due to replication of the vaccinia virus following vaccination against smallpox, and to treat monkeypox and cowpox in adults and children.8 Tecovirimat is available as both oral and intravenous formulations.10
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Tecovirimat (DB12020)
- Weight
- Average: 376.335
Monoisotopic: 376.10347684 - Chemical Formula
- C19H15F3N2O3
- Synonyms
- ST-246
- Tecovirimat
- External IDs
- SIGA-246
- ST 246
- ST-246
Pharmacology
- Indication
Tecovirimat is an inhibitor of the orthopoxvirus VP37 envelope wrapping protein and is indicated for the treatment of human smallpox disease in adults and pediatric patients weighing at least 3 kg. The efficacy of tecovirimat may be reduced in immunocompromised patients.10 In Europe, it is also indicated to treat complications due to replication of the vaccinia virus following vaccination against smallpox.8
In Europe, tecovirimat is also used to treat monkeypox and cowpox in adults and children.8
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 Complication of smallpox vaccination •••••••••••• ••••••••••• •••••• ••••••••• •••• •••••• •• •• •• ••• ••••••• •••••••• •••••••••••• ••••••• Treatment of Cow pox •••••••••••• ••••••••••• •••••• ••••••••• •••• •••••• •• •• •• ••• •••••• ••••••• Treatment of Monkeypox •••••••••••• ••••••••••• •••••• ••••••••• •••• •••••• •• •• •• ••• •••••• ••••••• Treatment of Variola major (smallpox) •••••••••••• ••••••••••• •••••• ••••••••• •••• •••••• •• •• •• ••• •••••• ••••••• Treatment of Variola major (smallpox) •••••••••••• ••••••••••• •••••• ••••••••• •••••••• •• ••••• • •• •••••••• ••••••••• - 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
Tecovirimat is an antiviral drug that helps to prevent the spread of virus 10 and reduce viremia.2 It is effective against all orthopoxviruses tested in vitro, including variola or smallpox virus.1
- Mechanism of action
Successful viral replication leads to the formation of a number of infectious virion forms. Mature viruses are infectious but remain intracellularly until cell lysis. On the other hand, enveloped virion form is created when mature viruses wrap with late endosomal membranes. The formation of a wrapping complex for enveloped virions is mediated by the orthopoxvirus P37 protein.2 These egress-competent enveloped virions are released in a nonlytic fashion from the cell 2 and play an essential role in cell-to-cell and long-range dissemination of the virus in the host.1,8
The P37 protein is encoded by a highly conserved gene in all members of the orthopoxvirus genus.10 P37 interacts with the Rab9 GTPase and TIP47, which are components of late endosome-derived transport vesicles. Interaction of P37 and Rab9 GTPase and TIP47 leads to the formation of the virus-specific wrapping complex for enveloped virions.2 Tecovirimat is an inhibitor of P37: it blocks the interaction of P37 with Rab9 and TIP47, preventing the formation of the wrapping complex.1,2,8,10
Target Actions Organism AEnvelope protein F13 inhibitorVariola virus (isolate Human/India/Ind3/1967) - Absorption
Tecovirimat is readily absorbed following oral administration.2 Following oral administration of 600 mg tecovirimat in healthy adults, the mean steady-state AUC0-24hr was 29816 hr x ng/mL and the Cmax was 2159 ng/mL. Following intravenous administration of 200 mg tecovirimat every 12 hours, the mean steady-state AUC0-24hr was 39405 hr x ng/mL and the Cmax was 2630 ng/mL. The Tmax is about six hours.10 The steady-state is achieved within four to six days.3,10
The oral bioavailability of tecovirimat is increased when taken with food. A moderate fat and calories meal increased the drug exposure (AUC) by 39% when tecovirimat was orally administered in conjunction with food.8
- Volume of distribution
The volume of distribution was 383 L following intravenous administration of 200 mg tecovirimat and 1030 L following oral administration of 600 mg tecovirimat. The blood-to-plasma ratio ranges from 0.62 to 0.90.10
- Protein binding
Tecovirimat is 77-82% bound to human plasma proteins.10
- Metabolism
Tecovirimat undergoes hydrolysis mediated by UGT1A1 and UGT1A4.10 Major metabolites are metabolites M4 (N-{3,5-dioxo-4-azatetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-en-4-yl}amine), M5 (3,5-dioxo-4-aminotetracyclo[5.3.2.0{2,6}.0{8,10}]dodec-11-ene), and TFMBA (4 (trifluoromethyl) benzoic acid). None of the metabolites is pharmacologically active. None of the glucuronide conjugates was found as a major metabolite in plasma.8 The exact chemical structures of tecovirimat metabolites have not been fully characterized.
- Route of elimination
The major routes of elimination are through metabolism and renal elimination. Following oral administration, about 73% of the dose was excreted in urine, predominantly in the form of glucuronidated metabolites. About 23% of the dose was recovered in feces, predominantly as the unchanged parent drug.10,8 In urine, primary tecovirimat glucuronide conjugate and M4 glucuronide conjugate were the most abundant components accounting for means of 24.4% and 30.3% of dose, respectively.8
- Half-life
The elimination half-life (CV%) was 21 (45%) hours following intravenous administration of 200 mg tecovirimat and 19 (29%) hours following oral administration of 600 mg tecovirimat.10
- Clearance
The clearance rate was 13 L/h following intravenous administration of 200 mg tecovirimat and 31 L/h following oral administration of 600 mg tecovirimat.10
- 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
In single-dose toxicity studies, no LD50 has been reached even when tecovirimat was given at very high doses (2000 mg/kg) in mice or non-human primates.11 There is no clinical experience with overdosage of tecovirimat. In case of overdosage, patients should be monitored for any signs or symptoms of adverse effects. Hemodialysis is not expected to effectively remove tecovirimat in overdosed patients.10
- 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 softwareAbemaciclib The metabolism of Abemaciclib can be increased when combined with Tecovirimat. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Tecovirimat. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Tecovirimat. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Tecovirimat. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Tecovirimat. - Food Interactions
- Take with food. Take tecovirimat within 30 minutes of eating a fatty meal containing approximately 25 grams of fat.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Tecovirimat monohydrate SB96YO2BR8 1162664-19-8 QRHXYGPOQKLBJP-NPIFKJBVSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Tecovirimat Siga Capsule 200 mg Oral SIGA Technologies, Inc. 2022-05-04 Not applicable EU 
Tpoxx Injection, solution, concentrate 10 mg/1mL Intravenous SIGA Technologies, Inc. 2022-05-31 Not applicable US 
Tpoxx Capsule 200 mg Oral SIGA Technologies, Inc. 2022-04-07 Not applicable Canada 
Tpoxx Capsule 200 mg/1 Oral SIGA Technologies, Inc. 2018-08-31 Not applicable US
Categories
- ATC Codes
- J05AX24 — Tecovirimat
- Drug Categories
- Acids, Carbocyclic
- Amides
- Anti-Infective Agents
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antivirals for Systemic Use
- BCRP/ABCG2 Inhibitors
- Benzene Derivatives
- Benzoates
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 Inhibitors (weak)
- Cytochrome P-450 CYP2C8 Inducers
- Cytochrome P-450 CYP2C8 Inducers (weak)
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Direct Acting Antivirals
- Heterocyclic Compounds, Fused-Ring
- Imides
- Isoindoles
- Orthopoxvirus VP37 Envelope Wrapping Protein Inhibitor
- Phthalic Acids
- UGT1A1 Substrates
- UGT1A3 substrates
- UGT1A4 substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as isoindolones. These are aromatic polycyclic compounds that an isoindole bearing a ketone.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Isoindoles and derivatives
- Sub Class
- Isoindolines
- Direct Parent
- Isoindolones
- Alternative Parents
- Trifluoromethylbenzenes / Benzoic acids and derivatives / Benzoyl derivatives / Pyrrolidine-2-ones / Dicarboximides / Lactams / Carboxylic acid hydrazides / Azacyclic compounds / Organonitrogen compounds / Organofluorides show 4 more
- Substituents
- 2-pyrrolidone / Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzoic acid or derivatives / Benzoyl / Carbonyl group / Carboxylic acid derivative show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- F925RR824R
- CAS number
- 869572-92-9
- InChI Key
- CSKDFZIMJXRJGH-VWLPUNTISA-N
- InChI
- InChI=1S/C19H15F3N2O3/c20-19(21,22)9-3-1-8(2-4-9)16(25)23-24-17(26)14-10-5-6-11(13-7-12(10)13)15(14)18(24)27/h1-6,10-15H,7H2,(H,23,25)/t10-,11+,12+,13-,14-,15+
- IUPAC Name
- N-[(1R,2R,6S,7S,8S,10R)-3,5-dioxo-4-azatetracyclo[5.3.2.0^{2,6}.0^{8,10}]dodec-11-en-4-yl]-4-(trifluoromethyl)benzamide
- SMILES
- FC(F)(F)C1=CC=C(C=C1)C(=O)NN1C(=O)[C@H]2[C@H]([C@H]3C=C[C@@H]2[C@@H]2C[C@H]32)C1=O
References
- General References
- Grosenbach DW, Honeychurch K, Rose EA, Chinsangaram J, Frimm A, Maiti B, Lovejoy C, Meara I, Long P, Hruby DE: Oral Tecovirimat for the Treatment of Smallpox. N Engl J Med. 2018 Jul 5;379(1):44-53. doi: 10.1056/NEJMoa1705688. [Article]
- Grosenbach DW, Jordan R, Hruby DE: Development of the small-molecule antiviral ST-246 as a smallpox therapeutic. Future Virol. 2011 May;6(5):653-671. doi: 10.2217/fvl.11.27. [Article]
- Jordan R, Chinsangaram J, Bolken TC, Tyavanagimatt SR, Tien D, Jones KF, Frimm A, Corrado ML, Pickens M, Landis P, Clarke J, Marbury TC, Hruby DE: Safety and pharmacokinetics of the antiorthopoxvirus compound ST-246 following repeat oral dosing in healthy adult subjects. Antimicrob Agents Chemother. 2010 Jun;54(6):2560-6. doi: 10.1128/AAC.01689-09. Epub 2010 Apr 12. [Article]
- Mucker EM, Goff AJ, Shamblin JD, Grosenbach DW, Damon IK, Mehal JM, Holman RC, Carroll D, Gallardo N, Olson VA, Clemmons CJ, Hudson P, Hruby DE: Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox). Antimicrob Agents Chemother. 2013 Dec;57(12):6246-53. doi: 10.1128/AAC.00977-13. Epub 2013 Oct 7. [Article]
- FDA approves the first drug with an indication for treatment of smallpox [Link]
- FDA approves first smallpox indicated treatment [Link]
- BioSpace News: SIGA Announces Health Canada Regulatory Approval of Oral TPOXX® [Link]
- Summary of Product Characteristics: Tecovirimat (tecovirimat) oral capsules [Link]
- GlobeNewsWire News Release: SIGA Technologies Receives Approval from the European Medicines Agency for Tecovirimat [Link]
- FDA Approved Drug Products: TPOXX (tecovirimat) capsules, for oral use or injection, for intravenous use [Link]
- FDA ADVISORY COMMITTEE BRIEFING DOCUMENT: Tecovirimat for the Treatment of Smallpox Disease (May 1, 2018) [Link]
- External Links
- PubChem Compound
- 16124688
- PubChem Substance
- 347828336
- ChemSpider
- 17281586
- ChEMBL
- CHEMBL1257073
- ZINC
- ZINC000035323125
- Wikipedia
- Tecovirimat
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 Available Not Available Monkeypox / Variola Major (Smallpox) 1 somestatus stop reason just information to hide Not Available Available Not Available Orthopox virus infection 1 somestatus stop reason just information to hide Not Available Withdrawn Not Available Variola Major (Smallpox) 1 somestatus stop reason just information to hide 4 Completed Other Variola Major (Smallpox) 2 somestatus stop reason just information to hide 4 Recruiting Treatment Monkeypox 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 200 mg Capsule Oral 200 mg/1 Injection, solution, concentrate Intravenous 10 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7737168 No 2010-06-15 2027-05-03 US US8802714 No 2014-08-12 2024-06-18 US US8530509 No 2013-09-10 2024-06-18 US US9339466 No 2016-05-17 2031-03-23 US US8124643 No 2012-02-28 2024-06-18 US US8039504 No 2011-10-18 2027-07-23 US US9907859 No 2018-03-06 2031-08-02 US US9233097 No 2016-01-12 2031-08-02 US US10576165 No 2020-03-03 2031-08-02 US US11890270 No 2012-08-08 2032-08-08 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 196 https://www.ema.europa.eu/en/documents/assessment-report/tecovirimat-siga-epar-public-assessment-report_en.pdf water solubility <1 mg/mL https://www.selleck.cn/msds/MSDS_S3380.pdf - Predicted Properties
Property Value Source Water Solubility 0.021 mg/mL ALOGPS logP 2.03 ALOGPS logP 2.07 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 9.15 Chemaxon pKa (Strongest Basic) -6.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 66.48 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 89.45 m3·mol-1 Chemaxon Polarizability 34.02 Å3 Chemaxon Number of Rings 5 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-00xr-1902000000-33811607cbbf75d30d1c Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-dc9ca1d3fb76988bbfe5 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0009000000-d3df5227be55f614408a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-004r-0209000000-4c3cf9bd3fdddacaface Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0409000000-9205e6b973185852af86 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-014r-1900000000-97205f6dd8015a6ba29c Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00or-0897000000-d6feedd9e70279e61ff5 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]- 184.10957 predictedDeepCCS 1.0 (2019) [M+H]+ 186.02293 predictedDeepCCS 1.0 (2019) [M+Na]+ 191.98979 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Variola virus (isolate Human/India/Ind3/1967)
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Major envelope protein that plays a role in the biogenesis of the viral double membrane and in egress of virus from the host cell. Produces the wrapped form of virus that is required for cell-to-cell spread. Acts as a lipase with broad specificity including phospholipase C, phospholipase A, and triacylglycerol lipase activities.
- Specific Function
- hydrolase activity
- Gene Name
- Not Available
- Uniprot ID
- P33815
- Uniprot Name
- Envelope protein F13
- Molecular Weight
- 41902.245 Da
References
- Duraffour S, Andrei G, Snoeck R: Tecovirimat, a p37 envelope protein inhibitor for the treatment of smallpox infection. IDrugs. 2010 Mar;13(3):181-91. [Article]
- Mucker EM, Goff AJ, Shamblin JD, Grosenbach DW, Damon IK, Mehal JM, Holman RC, Carroll D, Gallardo N, Olson VA, Clemmons CJ, Hudson P, Hruby DE: Efficacy of tecovirimat (ST-246) in nonhuman primates infected with variola virus (Smallpox). Antimicrob Agents Chemother. 2013 Dec;57(12):6246-53. doi: 10.1128/AAC.00977-13. Epub 2013 Oct 7. [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: TPOXX (tecovirimat) capsules, for oral use or injection, for intravenous use [Link]
Enzymes
- 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
- 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:15472229, PubMed:18674515, PubMed:18719240, PubMed:23288867, PubMed:23756265, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:23756265). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229, PubMed:18719240, PubMed:23288867). 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 calcidiol, which is the major circulating form of vitamin D3, essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonists losartan, candesartan and zolarsartan, which can inhibit the effect of angiotensin II (PubMed:18674515)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1A3
- Molecular Weight
- 60337.835 Da
References
- Summary of Product Characteristics: Tecovirimat (tecovirimat) oral capsules [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:18177842, PubMed:24641623). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:18177842). Involved in the glucuronidation of calcidiol, which is the major circulating form of vitamin D3 essential for the regulation of calcium and phosphate homeostasis (PubMed:24641623). Also glucuronidates the biologically active form of vitamin D3, calcitriol, probably leading to its biliary transport and intestinal reabsorption (PubMed:18177842)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1A4
- Molecular Weight
- 60024.535 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- Curator comments
- Tecovirimat and its M4 metabolite are inducers of cytochrome P450 (CYP)3A.
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). 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:11093772, PubMed:14559847, PubMed:15766564, PubMed:19965576, PubMed:7574697). Primarily catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) with a preference for the last double bond (PubMed:15766564, PubMed:19965576, PubMed:7574697). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes all trans-retinoic acid toward its 4-hydroxylated form (PubMed:11093772). Displays 16-alpha hydroxylase activity toward estrogen steroid hormones, 17beta-estradiol (E2) and estrone (E1) (PubMed:14559847). Plays a role in the oxidative metabolism of xenobiotics. It is the principal enzyme responsible for the metabolism of the anti-cancer drug paclitaxel (taxol) (PubMed:26427316)
- Specific Function
- arachidonic acid epoxygenase activity
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). 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:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
- Specific Function
- (R)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55944.565 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inducer
- Curator comments
- Tecovirimat and its M4 metabolite are inducers of cytochrome P450 (CYP)2B6.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:12865317, PubMed:21289075). 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 epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:12865317, PubMed:21289075). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850)
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Summary of Product Characteristics: Tecovirimat (tecovirimat) oral capsules [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Tecovirimat inhibited Breast Cancer Resistance Protein (BCRP) in vitro.
- General Function
- Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Molecular Weight
- 72313.47 Da
References
- FDA Approved Drug Products: TPOXX (tecovirimat) capsules, for oral use or injection, for intravenous use [Link]
Drug created at October 20, 2016 21:11 / Updated at September 02, 2022 17:58