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Identification
- Summary
Voclosporin is a calcineurin inhibitor for the treatment of lupus nephritis (LN) in patients diagnosed with systemic lupus erythematosus (SLE).
- Brand Names
- Lupkynis
- Generic Name
- Voclosporin
- DrugBank Accession Number
- DB11693
- Background
Lupus nephritis (LN) is a type of glomerulonephritis occurring in patients with systemic lupus erythematosus (SLE). LN is a significant cause of renal failure, morbidity, and death in patients with SLE. Within 10 years of being diagnosed with SLE, 5-20% of those suffering from LN develop end-stage kidney disease, a fatal condition. Early and accurate intervention for LN is important in improving clinical outcomes.2
Voclosporin, marketed as Lupkynis, is a calcineurin-inhibitor immunosuppressant for the treatment of LN.6 This cyclosporine A analog was approved by the FDA on January 22, 2021 following promising results in clinical trials. Early intervention with voclosporin coupled with a kidney response is believed to prevent irreversible damage to the kidney and lead to better long-term clinical outcomes for patients with LN.5 Voclosporin has demonstrated a more stable pharmacokinetic and pharmacodynamic relationship than cyclosporine, a higher potency than cyclosporine, and an improved metabolic profile when compared to older calcineurin inhibitors.9
In July 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended voclosporin be granted marketing authorization for use in combination with mycophenolate mofetil for the treatment of adult patients with active lupus nephritis.10
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Voclosporin (DB11693)
- Weight
- Average: 1214.646
Monoisotopic: 1213.841368058 - Chemical Formula
- C63H111N11O12
- Synonyms
- Voclosporin
- External IDs
- ISA-247
- ISA247
- ISATX-247
- ISATX247
- LX-211
- LX211
- R 1524
Pharmacology
- Indication
Voclosporin is used in combination with a background immunosuppressive regimen for the treatment of lupus nephritis. Safety has not been established in combination with cyclophosphamide.6
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 Adjunct therapy in treatment of Nephritis, lupus •••••••••••• ••••••• - 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
Voclosporin inhibits calcineurin, leading to the inhibition of T cell activation by blocking the transcription of early inflammatory cytokines. This reduces inflammation in the kidney, treating lupus nephritis and preventing permanent renal damage.6,7
- Mechanism of action
Through the inhibition of calcineurin, voclosporin blocks IL-2 expression and T-cell mediated immune responses, stabilizing podocytes in the kidneys.9
Voclospoprin is a cyclosporine A analog. It is structurally similar to cyclosporine A (CsA) with the exception of an amino acid modification in one region. This modification changes the binding of voclosporin to calcineurin. Cyclosporine inhibitors reversibly inhibit T-lymphocytes. They also inhibit lymphokine production and release. Cyclosporine A exerts its inhibitory effects on T-lymphocytes by binding to cyclophilin. A cyclophilin-cyclosporine complex is formed, leading to the inhibition of calcium- and calmodulin-dependent serine-threonine phosphatase activity of calcineurin. Along with calcineurin inhibition, the inhibition of many transcription factors necessary for the induction of various cytokine genes such as IL-2, IFN-γ, IL-4 and GM-CSF occurs. This, in turn, reduces inflammation, treating renal glomerulonephritis associated with systemic lupus erythematosus.3,8
Target Actions Organism AGuided entry of tail-anchored proteins factor CAMLG binderHumans AProtein phosphatase 3 catalytic subunit alpha inhibitorHumans ACalcineurin subunit B type 1 inhibitorHumans ACalcineurin subunit B type 2 inhibitorHumans - Absorption
When administered on an empty stomach, the median Tmax of voclosporin is 1.5 hours, but can range from 1-4 hours.6 The AUC is estimated at 7693.6 ng/mL*h and the Cmax is estimated at 955.5 ng/mL.1
- Volume of distribution
The apparent volume of distribution of voclosporin is 2,154 L. Voclosporin distributes extensively into red blood cells; distribution between whole blood and plasma is dependent on concentration and temperature.6
- Protein binding
The protein binding of voclosporin is approximately 97%.6
- Metabolism
Voclosporin is mainly metabolized by the CYP3A4 hepatic cytochrome enzyme. Pharmacologic activity is mainly attributed to the parent molecule. A major metabolite has been detected in human whole blood, representing 16.7% of total exposure; this metabolite is about 8-fold less potent than the parent drug, voclosporin.6,8
- Route of elimination
Voclosporin is eliminated in the urine and feces, with about 88% detected in the feces and about 2% detected in the urine.8
- Half-life
The average terminal half-life of voclosporin is about 30 hours (24.9 to 36.5 hours).6
- Clearance
The mean apparent steady-state clearance of voclosporin is 63.6 L/h.6 Hepatic and renal impairment significantly reduce the clearance of voclosporin.4
- 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
LD50 information for voclosporin is not readily available.
Accidental overdose with voclosporin has been reported with; symptoms of an overdose may include headache, nausea and vomiting, infections, tachycardia, urticaria, lethargy, and tremor. An increase in blood urea nitrogen, serum creatinine, and alanine aminotransferase levels is also possible. There is no known antidote to an overdose with voclosporin. If an overdose occurs, supportive and symptomatic treatment should be initiated, in addition to discontinuation of voclosporin. Assessment of blood urea nitrogen, serum creatinine, eGFR and alanine aminotransferase levels is recommended. Prescribing information suggests contacting a poison center or medical toxicologist for the management of an overdose with voclosporin.6
- 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 Voclosporin can be increased when it is combined with Abametapir. Abatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Voclosporin. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Voclosporin. Abrocitinib The serum concentration of Voclosporin can be increased when it is combined with Abrocitinib. Adagrasib The serum concentration of Voclosporin can be increased when it is combined with Adagrasib. - Food Interactions
- Avoid grapefruit products. Avoid food or drink containing grapefruit when taking voclosporin, as it may decrease metabolism and increase exposure to this drug.
- Take on an empty stomach. Take on an empty stomach, either 1 hour before or 2 hours after a meal and as close to 12 hours between doses as possible.
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
- Lupkynis (Aurinia Pharmaceuticals Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Lupkynis Capsule 7.9 mg Oral Otsuka Pharmaceutical Netherlands B.V. 2022-12-02 Not applicable EU 
Lupkynis Capsule 7.9 mg/1 Oral Aurinia Pharma U.S., Inc. 2021-01-22 Not applicable US 
Lupkynis Capsule 7.9 mg Oral Otsuka Pharmaceutical Netherlands B.V. 2023-02-08 Not applicable EU
Categories
- ATC Codes
- L04AD03 — Voclosporin
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antineoplastic and Immunomodulating Agents
- Calcineurin Inhibitor Immunosuppressant
- Calcineurin Inhibitors
- Cyclosporins
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Immunosuppressive Agents
- Organic Anion Transporting Polypeptide 1B1 Inhibitors
- Organic Anion Transporting Polypeptide 1B3 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- Peptides
- Peptides, Cyclic
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as cyclosporins. These are cyclic depsipeptides containing the cyclosporin backbone.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Peptidomimetics
- Sub Class
- Peptoid-peptide hybrids
- Direct Parent
- Cyclosporins
- Alternative Parents
- Oligopeptides / Macrolactams / Alpha amino acids and derivatives / Tertiary carboxylic acid amides / Secondary carboxylic acid amides / Secondary alcohols / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds show 3 more
- Substituents
- Alcohol / Aliphatic heteromonocyclic compound / Alpha-amino acid or derivatives / Alpha-oligopeptide / Azacycle / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Cyclosporin-backbone / Hydrocarbon derivative show 12 more
- Molecular Framework
- Aliphatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 2PN063X6B1
- CAS number
- 515814-01-4
- InChI Key
- BICRTLVBTLFLRD-PTWUADNWSA-N
- InChI
- InChI=1S/C63H111N11O12/c1-25-27-28-29-41(15)53(76)52-57(80)66-44(26-2)59(82)68(18)34-49(75)69(19)45(30-35(3)4)56(79)67-50(39(11)12)62(85)70(20)46(31-36(5)6)55(78)64-42(16)54(77)65-43(17)58(81)71(21)47(32-37(7)8)60(83)72(22)48(33-38(9)10)61(84)73(23)51(40(13)14)63(86)74(52)24/h25,27-28,35-48,50-53,76H,1,26,29-34H2,2-24H3,(H,64,78)(H,65,77)(H,66,80)(H,67,79)/b28-27+/t41-,42+,43-,44+,45+,46+,47+,48+,50+,51+,52+,53-/m1/s1
- IUPAC Name
- (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(1R,2R,4E)-1-hydroxy-2-methylhepta-4,6-dien-1-yl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-bis(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecone
- SMILES
- [H][C@@]1([C@H](O)[C@H](C)C\C=C\C=C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C(=O)[C@H](CC)NC1=O)C(C)C
References
- General References
- Li Y, Palmisano M, Sun D, Zhou S: Pharmacokinetic Disposition Difference Between Cyclosporine and Voclosporin Drives Their Distinct Efficacy and Safety Profiles in Clinical Studies. Clin Pharmacol. 2020 Jul 1;12:83-96. doi: 10.2147/CPAA.S255789. eCollection 2020. [Article]
- Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C: Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. doi: 10.1038/s41572-019-0141-9. [Article]
- Schultz C: Voclosporin as a treatment for noninfectious uveitis. Ophthalmol Eye Dis. 2013 May 5;5:5-10. doi: 10.4137/OED.S7995. Print 2013. [Article]
- Ling SY, Huizinga RB, Mayo PR, Freitag DG, Aspeslet LJ, Foster RT: Pharmacokinetics of voclosporin in renal impairment and hepatic impairment. J Clin Pharmacol. 2013 Dec;53(12):1303-12. doi: 10.1002/jcph.166. Epub 2013 Oct 8. [Article]
- Aurinia Pharmaceuticals Press Release: FDA Approves Aurinia Pharmaceuticals Lupkynis [Link]
- FDA Approved Products: LUPKYNIS (voclosporin) capsules, for oral use [Link]
- Toronto Research Chemicals MSDS: Voclosporin [Link]
- EMA Assessment Report: Luveniq (voclosporin) oral capsules [Link]
- Aurinia Pharmaceuticals press release: Aurinia Completes Voclosporin Drug-Drug Interaction Study Demonstrating No Clinically Significant Interaction With Mycophenolate Mofetil [Link]
- EMA CHMP Positive Opinion: Lupkynis (voclosporin) [Link]
- External Links
- PubChem Compound
- 6918486
- PubChem Substance
- 347828058
- ChemSpider
- 5293683
- ChEBI
- 135957
- Wikipedia
- Voclosporin
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 data3 Completed Treatment Anterior Uveitis (AU) / Panuveitis 1 somestatus stop reason just information to hide 3 Completed Treatment Lupus Nephritis 2 somestatus stop reason just information to hide 3 Completed Treatment Non-Infectious Uveitis 1 somestatus stop reason just information to hide 3 Completed Treatment Panuveitis / Posterior Uveitis / Uveitis, Intermediate 2 somestatus stop reason just information to hide 3 Completed Treatment Psoriasis 3 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Capsule Oral 7.9 mg Capsule Oral 7.9 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7332472 No 2008-02-19 2022-10-17 US US10286036 No 2019-05-14 2037-12-07 US US11622991 No 2017-12-07 2037-12-07 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) >129 https://www.scbt.com/p/voclosporin-d4-515814-01-4-unlabeled water solubility less than 0.1 g/L https://d1io3yog0oux5.cloudfront.net/auriniapharma/files/pages/lupkynis-prescribing-information/FPI-0011+Approved+USPI++MG.pdf logP 8.6 http://www.chemspider.com/Chemical-Structure.5293683.html pKa 13.32 ± 0.70 https://www.chemicalbook.com/ChemicalProductProperty_DE_CB42496083.htm - Predicted Properties
Property Value Source logP 3.78 Chemaxon pKa (Strongest Acidic) 11.83 Chemaxon pKa (Strongest Basic) -2.4 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 5 Chemaxon Polar Surface Area 278.8 Å2 Chemaxon Rotatable Bond Count 16 Chemaxon Refractivity 331.79 m3·mol-1 Chemaxon Polarizability 133.94 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 371.803 predictedDeepCCS 1.0 (2019) [M+H]+ 373.49277 predictedDeepCCS 1.0 (2019) [M+Na]+ 379.64963 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Binder
- General Function
- Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (PubMed:23041287, PubMed:24392163, PubMed:27226539). Required for the stability of GET1 (PubMed:32187542). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (PubMed:7522304). Essential for the survival of peripheral follicular B cells (By similarity)
- Specific Function
- Ubiquitin protein ligase binding
- Gene Name
- CAMLG
- Uniprot ID
- P49069
- Uniprot Name
- Guided entry of tail-anchored proteins factor CAMLG
- Molecular Weight
- 32952.255 Da
References
- Kuglstatter A, Mueller F, Kusznir E, Gsell B, Stihle M, Thoma R, Benz J, Aspeslet L, Freitag D, Hennig M: Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin). Acta Crystallogr D Biol Crystallogr. 2011 Feb;67(Pt 2):119-23. doi: 10.1107/S0907444910051905. Epub 2011 Jan 15. [Article]
- Schultz C: Voclosporin as a treatment for noninfectious uveitis. Ophthalmol Eye Dis. 2013 May 5;5:5-10. doi: 10.4137/OED.S7995. Print 2013. [Article]
- EMA Assessment Report: Luveniq (voclosporin) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals (PubMed:15671020, PubMed:18838687, PubMed:19154138, PubMed:23468591, PubMed:30254215). Many of the substrates contain a PxIxIT motif and/or a LxVP motif (PubMed:17498738, PubMed:17502104, PubMed:22343722, PubMed:23468591, PubMed:27974827). In response to increased Ca(2+) levels, dephosphorylates and activates phosphatase SSH1 which results in cofilin dephosphorylation (PubMed:15671020). In response to increased Ca(2+) levels following mitochondrial depolarization, dephosphorylates DNM1L inducing DNM1L translocation to the mitochondrion (PubMed:18838687). Positively regulates the CACNA1B/CAV2.2-mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Dephosphorylates heat shock protein HSPB1 (By similarity). Dephosphorylates and activates transcription factor NFATC1 (PubMed:19154138). In response to increased Ca(2+) levels, regulates NFAT-mediated transcription probably by dephosphorylating NFAT and promoting its nuclear translocation (PubMed:26248042). Dephosphorylates and inactivates transcription factor ELK1 (PubMed:19154138). Dephosphorylates DARPP32 (PubMed:19154138). May dephosphorylate CRTC2 at 'Ser-171' resulting in CRTC2 dissociation from 14-3-3 proteins (PubMed:30611118). Dephosphorylates transcription factor TFEB at 'Ser-211' following Coxsackievirus B3 infection, promoting nuclear translocation (PubMed:33691586). Required for postnatal development of the nephrogenic zone and superficial glomeruli in the kidneys, cell cycle homeostasis in the nephrogenic zone, and ultimately normal kidney function (By similarity). Plays a role in intracellular AQP2 processing and localization to the apical membrane in the kidney, may thereby be required for efficient kidney filtration (By similarity). Required for secretion of salivary enzymes amylase, peroxidase, lysozyme and sialic acid via formation of secretory vesicles in the submandibular glands (By similarity). Required for calcineurin activity and homosynaptic depotentiation in the hippocampus (By similarity). Required for normal differentiation and survival of keratinocytes and therefore required for epidermis superstructure formation (By similarity). Positively regulates osteoblastic bone formation, via promotion of osteoblast differentiation (By similarity). Positively regulates osteoclast differentiation, potentially via NFATC1 signaling (By similarity). May play a role in skeletal muscle fiber type specification, potentially via NFATC1 signaling (By similarity). Negatively regulates MAP3K14/NIK signaling via inhibition of nuclear translocation of the transcription factors RELA and RELB (By similarity). Required for antigen-specific T-cell proliferation response (By similarity). Dephosphorylates KLHL3, promoting the interaction between KLHL3 and WNK4 and subsequent degradation of WNK4 (PubMed:30718414). Negatively regulates SLC9A1 activity (PubMed:31375679)
- Specific Function
- Atpase binding
- Gene Name
- PPP3CA
- Uniprot ID
- Q08209
- Uniprot Name
- Protein phosphatase 3 catalytic subunit alpha
- Molecular Weight
- 58687.27 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity
- Specific Function
- Calcium ion binding
- Gene Name
- PPP3R1
- Uniprot ID
- P63098
- Uniprot Name
- Calcineurin subunit B type 1
- Molecular Weight
- 19299.785 Da
References
- EMA Assessment Report: Luveniq (voclosporin) oral capsules [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity
- Specific Function
- Calcium ion binding
- Gene Name
- PPP3R2
- Uniprot ID
- Q96LZ3
- Uniprot Name
- Calcineurin subunit B type 2
- Molecular Weight
- 19533.065 Da
References
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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
Drug created at October 20, 2016 20:40 / Updated at August 26, 2024 19:23