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Identification
- Summary
Deucravacitinib is a TYK2 inhibitor being investigated as a treatment for psoriasis.
- Brand Names
- Sotyktu
- Generic Name
- Deucravacitinib
- DrugBank Accession Number
- DB16650
- Background
Deucravacitinib is a novel oral selective tyrosine kinase 2 (TYK2) inhibitor. Unlike other Janus kinase 1/2/3 inhibitors that bind to the conserved active domain of these non-receptor tyrosine kinases, deucravacitinib binds to the regulatory domain of TYK2 with high selectivity to this therapeutic target.1,2 This selectivity towards TYK2 may lead to an improved safety profile of deucravacitinib, as nonselective JAK inhibitors are associated with a range of adverse effects such as altered cholesterol and triglyceride levels and liver and kidney dysfunction.2
Deucravacitinib was first approved by the FDA in September 2022 to treat moderate-to-severe plaque psoriasis.5 It was later approved by Health Canada in November 2022 6 and by the European Medicines Agency in March 2023.8
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Deucravacitinib (DB16650)
- Weight
- Average: 425.467
Monoisotopic: 425.200316838 - Chemical Formula
- C20H22N8O3
- Synonyms
- Deucravacitinib
- External IDs
- BMS-986165
- WHO 11342
Pharmacology
- Indication
Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is not recommended for use in combination with other potent immunosuppressants.5,6,7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Severe plaque psoriasis •••••••••••• ••••• •••••••••• ••• •••••••••••• •••••• Management of Severe plaque psoriasis •••••••••••• ••••• •••••••••• ••• •••••••• ••••••• ••• ••••••••• •••••• Management of Moderate plaque psoriasis •••••••••••• ••••• •••••••••• ••• •••••••••••• •••••• Management of Moderate plaque psoriasis •••••••••••• ••••• •••••••••• ••• •••••••• ••••••• ••• ••••••••• •••••• - Contraindications & Blackbox Warnings
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Deucravacitinib is a tyrosine kinase 2 (TYK2) inhibitor that works to suppress the immune signaling pathways in inflammatory disorders, such as plaque psoriasis. In clinical studies comprising patients with psoriasis, deucravacitinib reduced psoriasis-associated gene expression in psoriatic skin in a dose dependent manner, including reductions in IL-23-pathway and type I IFN pathway regulated genes. Following 16 weeks of once-daily treatment, deucravacitinib reduced inflammatory markers such as IL-17A, IL-19 and beta-defensin by 47 to 50%, 72%, and 81 to 84%, respectively.5 Deucravacitinib does not affect with JAK2-dependent hematopoietic functions.4
- Mechanism of action
Tyrosine kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of kinases, which are intracellular tyrosine kinases that activate the JAK–signal transducer and activator of the transcription pathway. Unlike other members of the JAK family that promote broader immune and extra-immune pathways, such as lipid metabolism, the TYK2 signalling pathway is responsible for selected immune pathways.1 TYK2 mediates the signalling of inflammatory cytokines of both adaptive (e.g., interleukin (IL) 12 and IL-23) and innate (e.g., type I interferons) immune responses.3 IL-23 has been implicated in the pathogenesis of immune-mediated disorders such as psoriasis and psoriatic arthritis.1 It activates and promotes the proliferation of Th17 cells: subsequently, Th17 cells secrete inflammatory mediators, such as IL-17 and tumour necrosis factor-alpha, that stimulate epidermal cells to produce cytokines and chemokines that attract and activate innate immune system cells.1,2 Enhanced activity of Th17 cells leads to sustained inflammatory responses in the skin and joints as manifested in psoriatic arthritis.1
Deucravacitinib inhibits TYK2 via an allosteric mechanism: it binds to the enzyme's regulatory domain - also known as the pseudokinase (JH2) domain - instead of the catalytic domain. This binding activity allows high selectivity towards TYK2 over other tyrosine kinase enzymes. In in vitro cellular assays, deucravacitinib showed a 100-fold to 2000-fold selectivity for TYK2 over JAK 1/2/3 and demonstrated minimal or no activity against JAK 1/2/3. Upon binding to TYK2, deucravacitinib induces a conformational change and locks the regulatory domain of TYK2 into an inhibitory confirmation with the catalytic domain, trapping TYK2 in an inactive state.1,2 Inhibiting TYK2 leads to the downregulation of the IL-23/TH17 pathway, IL-12 signalling, type 1 interferon pathway, and keratinocyte activation.3
Target Actions Organism ANon-receptor tyrosine-protein kinase TYK2 inhibitorHumans - Absorption
Following oral administration, deucravacitinib plasma Cmax and AUC increased proportionally over a dose range from 3 mg to 36 mg (0.5 to 6 times the approved recommended dosage) in healthy subjects. The steady state Cmax and AUC24 of deucravacitinib following administration of 6 mg once daily were 45 ng/mL and 473 ng x hr/mL, respectively. The steady state Cmax and AUC24 of the active deucravacitinib metabolite, BMT-153261, following administration of 6 mg once daily were 5 ng/mL and 95 ng x hr/mL, respectively. The absolute oral bioavailability of deucravacitinib was 99% and the median Tmax ranged from two to three hours.5
A high-fat, high-calorie meal decreased Cmax and AUC of deucravacitinib by 24% and 11%, respectively, and prolonged Tmax by one hour; however, this has clinically significant effects on drug absorption and exposure.5
- Volume of distribution
The volume of distribution of deucravacitinib at steady state is 140 L.5
- Protein binding
Protein binding of deucravacitinib was 82 to 90% and the blood-to-plasma concentration ratio was 1.26.5
- Metabolism
Deucravacitinib undergoes N-demethylation mediated by cytochrome P-450 (CYP) 1A2 to form major metabolite BMT-153261, which has a comparable pharmacological activity to the parent drug. However, the circulating exposure of BMT-153261 accounts for approximately 20% of the systemic exposure of the total drug-related components. Deucravacitinib is also metabolized by CYP2B6, CYP2D6, carboxylesterase (CES) 2, and uridine glucuronyl transferase (UGT) 1A9.5
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- Route of elimination
After a single dose of radiolabeled deucravacitinib, approximately 13% and 26% of the dose was recovered as unchanged in urine and feces, respectively. Approximately 6% and 12% of the dose was detected as BMT-153261 in urine and feces, respectively.5
- Half-life
The terminal half-life of deucravacitinib was 10 hours.5
- Clearance
The renal clearance of deucravacitinib ranged from 27 to 54 mL/minute.5
- Adverse Effects
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No information regarding the acute toxicity profile and LD50 of deucravacitinib is available. There is no experience regarding human overdosage with deucravacitinib. There is no known antidote for deucravacitinib overdose and hemodialysis is unlikely to be effective, as the extent of deucravacitinib elimination by hemodialysis is small (5.4% of dose per dialysis treatment).5
- 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 softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Deucravacitinib. Acetaminophen The serum concentration of Acetaminophen can be increased when it is combined with Deucravacitinib. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Deucravacitinib. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Deucravacitinib. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Deucravacitinib. - Food Interactions
- Take with or without food. Food has no clinically significant effect on drug absorption and exposure.
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 Deucravacitinib hydrochloride 95C5558CF4 1609392-28-0 LILQGPVDQZORJG-NIIDSAIPSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Sotyktu Tablet, film coated 6 mg Oral Bristol Myers Squibb Pharma Eeig 2023-04-04 Not applicable EU 
Sotyktu Tablet 6 mg Oral Bristol Myers Squibb 2023-02-14 Not applicable Canada 
Sotyktu Tablet, film coated 6 mg Oral Bristol Myers Squibb Pharma Eeig 2023-04-04 Not applicable EU Sotyktu Tablet, film coated 6 mg Oral Bristol Myers Squibb Pharma Eeig 2023-04-04 Not applicable EU Sotyktu Tablet, film coated 6 mg/1 Oral E.R. Squibb & Sons, L.L.C. 2022-09-09 Not applicable US 
Categories
- ATC Codes
- L04AF07 — Deucravacitinib
- Drug Categories
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Substrates
- Dermatologicals
- Enzyme Inhibitors
- Immunosuppressive Agents
- Janus Kinase Inhibitor
- Janus Kinase Inhibitors
- OATP1B3 inhibitors
- OCT1 substrates
- P-glycoprotein substrates
- Protein Kinase Inhibitors
- Selective Immunosuppressants
- Tyrosine Kinase 2 Inhibitor
- Tyrosine Kinase Inhibitors
- UGT1A9 Substrates
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- N0A21N6RAU
- CAS number
- 1609392-27-9
- InChI Key
- BZZKEPGENYLQSC-FIBGUPNXSA-N
- InChI
- InChI=1S/C20H22N8O3/c1-21-20(30)16-14(9-15(25-26-16)24-19(29)11-7-8-11)23-13-6-4-5-12(17(13)31-3)18-22-10-28(2)27-18/h4-6,9-11H,7-8H2,1-3H3,(H,21,30)(H2,23,24,25,29)/i1D3
- IUPAC Name
- 6-cyclopropaneamido-4-{[2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl]amino}-N-(2H3)methylpyridazine-3-carboxamide
- SMILES
- [2H]C([2H])([2H])NC(=O)C1=C(NC2=CC=CC(C3=NN(C)C=N3)=C2OC)C=C(NC(=O)C2CC2)N=N1
References
- General References
- Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, Kim J, Singhal S, Nowak M, Banerjee S: Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022 Mar 3. pii: annrheumdis-2021-221664. doi: 10.1136/annrheumdis-2021-221664. [Article]
- Chimalakonda A, Burke J, Cheng L, Catlett I, Tagen M, Zhao Q, Patel A, Shen J, Girgis IG, Banerjee S, Throup J: Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. Dermatol Ther (Heidelb). 2021 Oct;11(5):1763-1776. doi: 10.1007/s13555-021-00596-8. Epub 2021 Aug 30. [Article]
- Catlett IM, Hu Y, Gao L, Banerjee S, Gordon K, Krueger JG: Molecular and clinical effects of selective tyrosine kinase 2 inhibition with deucravacitinib in psoriasis. J Allergy Clin Immunol. 2021 Nov 10. pii: S0091-6749(21)01690-0. doi: 10.1016/j.jaci.2021.11.001. [Article]
- Le AM, Puig L, Torres T: Deucravacitinib for the Treatment of Psoriatic Disease. Am J Clin Dermatol. 2022 Aug 12. pii: 10.1007/s40257-022-00720-0. doi: 10.1007/s40257-022-00720-0. [Article]
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Health Canada Approved Drug Products: SOTYKTU (deucravacitinib) Oral Tablets [Link]
- EMA Approved Drug Products: Sotyktu (deucravacitinib) Oral Tablets [Link]
- Bristol Myers Squibb: Bristol Myers Squibb Receives European Commission Approval of Sotyktu (deucravacitinib), a Once-Daily Oral Treatment for Adults With Moderate-to-Severe Plaque Psoriasis [Link]
- External Links
- ChemSpider
- 72380005
- BindingDB
- 50507816
- 2612087
- ChEMBL
- CHEMBL4435170
- Wikipedia
- Deucravacitinib
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 Not Yet Recruiting Not Available Psoriasis Vulgaris (Plaque Psoriasis) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Moderate to Severe Plaque Psoriasis 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Psoriasis 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Psoriasis Vulgaris (Plaque Psoriasis) 2 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Psoriasis 2 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 6 mg Tablet Oral 6.000 mg Tablet, film coated Oral 6 mg/1 Tablet, film coated Oral 6 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US11021475 No 2021-06-01 2033-11-07 US USRE47929 No 2020-04-07 2033-11-07 US US10000480 No 2018-06-19 2033-11-07 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.159 mg/mL ALOGPS logP 1.8 ALOGPS logP 2.1 Chemaxon logS -3.4 ALOGPS pKa (Strongest Acidic) 11.09 Chemaxon pKa (Strongest Basic) 2.38 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 135.95 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 138.38 m3·mol-1 Chemaxon Polarizability 44.49 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No 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 splash10-00di-0001900000-a66ffc24d04789987c14 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00ei-0019200000-780f6d8a0e47c880ff66 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00r6-0009300000-02405db2c838b5b62d8e Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0009000000-c353dca0ca346d16dd77 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0kov-0039200000-5474ab3cffaa5dc56650 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0029000000-c81a5fa1dca92c9d8d24 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Tyrosine kinase of the non-receptor type involved in numerous cytokines and interferons signaling, which regulates cell growth, development, cell migration, innate and adaptive immunity (PubMed:10542297, PubMed:10995743, PubMed:7657660, PubMed:7813427, PubMed:8232552). Plays both structural and catalytic roles in numerous interleukins and interferons (IFN-alpha/beta) signaling (PubMed:10542297). Associates with heterodimeric cytokine receptor complexes and activates STAT family members including STAT1, STAT3, STAT4 or STAT6 (PubMed:10542297, PubMed:7638186). The heterodimeric cytokine receptor complexes are composed of (1) a TYK2-associated receptor chain (IFNAR1, IL12RB1, IL10RB or IL13RA1), and (2) a second receptor chain associated either with JAK1 or JAK2 (PubMed:10542297, PubMed:25762719, PubMed:7526154, PubMed:7813427). In response to cytokine-binding to receptors, phosphorylates and activates receptors (IFNAR1, IL12RB1, IL10RB or IL13RA1), creating docking sites for STAT members (PubMed:7526154, PubMed:7657660). In turn, recruited STATs are phosphorylated by TYK2 (or JAK1/JAK2 on the second receptor chain), form homo- and heterodimers, translocate to the nucleus, and regulate cytokine/growth factor responsive genes (PubMed:10542297, PubMed:25762719, PubMed:7657660). Negatively regulates STAT3 activity by promototing phosphorylation at a specific tyrosine that differs from the site used for signaling (PubMed:29162862)
- Specific Function
- ATP binding
- Gene Name
- TYK2
- Uniprot ID
- P29597
- Uniprot Name
- Non-receptor tyrosine-protein kinase TYK2
- Molecular Weight
- 133648.77 Da
References
- Mease PJ, Deodhar AA, van der Heijde D, Behrens F, Kivitz AJ, Neal J, Kim J, Singhal S, Nowak M, Banerjee S: Efficacy and safety of selective TYK2 inhibitor, deucravacitinib, in a phase II trial in psoriatic arthritis. Ann Rheum Dis. 2022 Mar 3. pii: annrheumdis-2021-221664. doi: 10.1136/annrheumdis-2021-221664. [Article]
- Chimalakonda A, Burke J, Cheng L, Catlett I, Tagen M, Zhao Q, Patel A, Shen J, Girgis IG, Banerjee S, Throup J: Selectivity Profile of the Tyrosine Kinase 2 Inhibitor Deucravacitinib Compared with Janus Kinase 1/2/3 Inhibitors. Dermatol Ther (Heidelb). 2021 Oct;11(5):1763-1776. doi: 10.1007/s13555-021-00596-8. Epub 2021 Aug 30. [Article]
- Catlett IM, Hu Y, Gao L, Banerjee S, Gordon K, Krueger JG: Molecular and clinical effects of selective tyrosine kinase 2 inhibition with deucravacitinib in psoriasis. J Allergy Clin Immunol. 2021 Nov 10. pii: S0091-6749(21)01690-0. doi: 10.1016/j.jaci.2021.11.001. [Article]
- Le AM, Puig L, Torres T: Deucravacitinib for the Treatment of Psoriatic Disease. Am J Clin Dermatol. 2022 Aug 12. pii: 10.1007/s40257-022-00720-0. doi: 10.1007/s40257-022-00720-0. [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: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:10681376, PubMed:11555828, PubMed:12865317, PubMed:19965576, PubMed:9435160). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:11555828, PubMed:12865317). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2 (PubMed:11555828, PubMed:12865317). Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid (PubMed:10681376). Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer (PubMed:19965576). Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA (PubMed:9435160). May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (PubMed:21068195). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin (PubMed:14725854). Metabolizes caffeine via N3-demethylation (Probable)
- Specific Function
- aromatase activity
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58406.915 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, 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) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
- Specific Function
- anandamide 11,12 epoxidase activity
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- The alternate name for this enzyme is carboxylesterase (CES) 2.
- General Function
- Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs (PubMed:9169443). Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and 6-monoacetylmorphine (PubMed:9169443). Hydrolyzes aspirin, substrates with large alcohol group and small acyl group and endogenous lipids such as triacylglycerol (PubMed:28677105). Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes of 2-arachidonoylglycerol and prostaglandins (PubMed:21049984)
- Specific Function
- carboxylesterase activity
- Gene Name
- CES2
- Uniprot ID
- O00748
- Uniprot Name
- Cocaine esterase
- Molecular Weight
- 61806.41 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [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:15470161, PubMed:15472229, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of 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 caderastan, 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:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212)
- Specific Function
- enzyme binding
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1A9
- Molecular Weight
- 59940.495 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
- Specific Function
- ABC-type xenobiotic transporter activity
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- ATP-dependent translocase ABCB1
- Molecular Weight
- 141477.255 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- 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: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:11388889, PubMed:11408531, PubMed:12439218, PubMed:12719534, PubMed:15389554, PubMed:16263091, PubMed:16272756, PubMed:16581093, PubMed:19536068, PubMed:21128598, PubMed:23680637, PubMed:24961373, PubMed:34040533, PubMed:9187257, PubMed:9260930, PubMed:9655880). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation (PubMed:16263091). Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, histamine, neurotransmitters dopamine, serotonin and adrenaline (PubMed:12439218, PubMed:24961373, PubMed:35469921, PubMed:9260930). Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover (PubMed:21128598). Involved in the hepatic uptake of vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism (PubMed:24961373). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with lower efficency (PubMed:17460754). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (Probable). Also involved in the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:11408531, PubMed:15389554, PubMed:35469921, PubMed:9260930)
- Specific Function
- (R)-carnitine transmembrane transporter activity
- Gene Name
- SLC22A1
- Uniprot ID
- O15245
- Uniprot Name
- Solute carrier family 22 member 1
- Molecular Weight
- 61153.345 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Mediates the Na(+)-independent uptake of organic anions (PubMed:10779507, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:10779507, PubMed:11159893, PubMed:12568656, PubMed:15159445, PubMed:17412826, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16624871, PubMed:16627748)
- Specific Function
- bile acid transmembrane transporter activity
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
References
- FDA Approved Drug Products: SOTYKTU (deucravacitinib) tablets, for oral use [Link]
Drug created at March 24, 2021 22:54 / Updated at April 07, 2023 13:12