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Identification
- Summary
Baricitinib is a Janus kinase inhibitor used to treat moderate to severe rheumatoid arthritis that has responded poorly to at least one TNF antagonist.
- Brand Names
- Olumiant
- Generic Name
- Baricitinib
- DrugBank Accession Number
- DB11817
- Background
Baricitinib is a Janus kinase (JAK) inhibitor. JAKs are tyrosine protein kinases that play an important role in pro-inflammatory signaling pathways. Overactive JAKs have been implicated in autoimmune disorders, such as rheumatoid arthritis. By inhibiting the actions of JAK1 and JAK2, baricitinib attenuates JAK-mediated inflammation and immune responses.9
Baricitinib was first approved by the European Commission (EC) in February 2017 for the treatment of rheumatoid arthritis in adults 4 and was later approved by the FDA in 2018.5 The EC later approved baricitinib for the treatment of atopic dermatitis, making it the first JAK inhibitor used for this indication in Europe.6 While baricitinib was granted emergency use as a treatment for COVID-19 in combination with remdesivir under the Emergency Use Authorization (EUA) in November 2020,8 the FDA fully approved the use of baricitinib for the treatment of COVID-19 in May 2022.9
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Baricitinib (DB11817)
- Weight
- Average: 371.42
Monoisotopic: 371.116443989 - Chemical Formula
- C16H17N7O2S
- Synonyms
- Baricitinib
- External IDs
- INCB-028050
- INCB028050
- LY-3009104
- LY3009104
Pharmacology
- Indication
In the US and Europe, baricitinib is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF blockers. Baricitinib may be used as monotherapy or in combination with methotrexate 9,11 or other DMARDs.9
In Europe, baricitinib is indicated for the treatment of moderate to severe atopic dermatitis in adult patients who are candidates for systemic therapy.11
In the US, baricitinib is also indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adults requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation.9 Recently, it is also approved as the treatment for severe alopecia areata in adults.12
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 Management of Alopecia areata (aa) •••••••••••• ••••• •••••• Treatment of Coronavirus disease 2019 (covid‑19) •••••••••••• ••••• •••••••••• •••••••••••• •••••••••••• •••••• Treatment of Coronavirus disease 2019 (covid‑19) •••••••••••• ••••• ••••••••••••• •••••••••••••• •••••••• ••••••••••• •••••• •••••• Treatment of Coronavirus disease 2019 (covid‑19) •••••••••••• ••••• ••••••••• •••••••••••• ••••••• •••••••••••• •••••• Used in combination to treat Novel coronavirus infectious disease (covid-19) Regimen in combination with: Remdesivir (DB14761) ••• ••••• ••••••••••• ••••••••• •••••••••• •••••••••••• •••••••••••• •••••• - Contraindications & Blackbox Warnings
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Baricitinib is a disease-modifying antirheumatic drug (DMARD) used to ameliorate symptoms and slow down the progression of rheumatoid arthritis. In animal models of inflammatory arthritis, baricitinib was shown to have significant anti-inflammatory effects but also led to the preservation of cartilage and bone, with no detectable suppression of humoral immunity or adverse hematologic effects.1 Baricitinib decreased the levels of immunoglobulins and serum C-reactive protein in patients with rheumatoid arthritis.9
- Mechanism of action
As members of the tyrosine kinase family, Janus kinases (JAKs) are intracellular enzymes that modulate signals from cytokines and growth factor receptors involved in hematopoiesis, inflammation, and immune cell function. Upon binding of extracellular cytokines and growth factors, JAKs phosphorylate and activate Signal Transducers and Activators of Transcription (STATs). STATs modulate intracellular activity, including gene transcription of inflammatory mediators that promote an autoimmune response,2,3,7,9 such as IL-2, IL-6, IL-12, IL-15, IL-23, IFN-γ, GM-CSF, and interferons.2,3 The JAK-STAT pathway has been implicated in the pathophysiology of rheumatoid arthritis, as it is associated with an overproduction of inflammatory mediators.3
There are four JAK proteins: JAK 1, JAK 2, JAK 3 and TYK2. JAKs form homodimers or heterodimers and pair differently in different cell receptors to transmit cytokine signaling.7,9 Baricitinib is a selective and reversible inhibitor of JAK1 and JAK2 with less affinity for JAK3 and TYK2; however, the relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.9 Baricitinib inhibits the activity of JAK proteins and modulates the signaling pathway of various interleukins, interferons, and growth factors. It was also shown to decrease the proliferation of JAK1/JAK2 expression in mutated cells and induce cell apoptosis.7
Target Actions Organism ATyrosine-protein kinase JAK1 inhibitorHumans ATyrosine-protein kinase JAK2 inhibitorHumans ATyrosine-protein kinase JAK3 inhibitorHumans UNon-receptor tyrosine-protein kinase TYK2 inhibitorHumans - Absorption
The absolute bioavailability of baricitinib is approximately 80%. The Cmax was reached after one hour of oral drug administration. A high-fat meal decreased the mean AUC and Cmax of baricitinib by approximately 11% and 18%, respectively, and delayed Tmax by 0.5 hours.9
- Volume of distribution
Following intravenous administration, the volume of distribution was 76 L, indicating distribution into tissues.9
- Protein binding
Baricitinib is approximately 50% bound to plasma proteins and 45% bound to serum proteins.9
- Metabolism
Baricitinib is metabolized by CYP3A4. Approximately 6% of the orally administered dose was identified as metabolites in urine and feces; however, no metabolites of baricitinib were quantifiable in plasma.9
- Route of elimination
Baricitinib is predominantly excreted via renal elimination. It is cleared via filtration and active secretion. Approximately 75% of the administered dose was eliminated in the urine, with 20% of that dose being the unchanged drug. About 20% of the dose was eliminated in the feces, with 15% of that dose being an unchanged drug.9
- Half-life
The elimination half-life in patients with rheumatoid arthritis is approximately 12 hours. The elimination half-life was 10.8 hours in intubated patients with COVID-19 who received baricitinib via nasogastric (NG) or orogastric (OG) tube.9
- Clearance
The total body clearance of baricitinib was 8.9 L/h in patients with rheumatoid arthritis. The total body clearance and half-life of baricitinib was 14.2 L/h in intubated patients with COVID-19 who received baricitinib via nasogastric (NG) or orogastric (OG) tube.9
- 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
The oral lowest published toxic dose (TDLo) is 1820 g/kg in mice and 5096 g/kg in rats.10
In clinical trials, single doses up to 40 mg and multiple doses of up to 20 mg daily for 10 days did not result in any dose-limiting toxicity. Pharmacokinetic data of a single dose of 40 mg in healthy volunteers indicate that more than 90% of the administered dose is expected to be eliminated within 24 hours. In case of an overdose, it is recommended that patients are monitored for signs and symptoms of drug-related adverse reactions, which should be responded with appropriate treatment.9
- 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 softwareAbacavir Abacavir may decrease the excretion rate of Baricitinib which could result in a higher serum level. Abametapir The serum concentration of Baricitinib 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 Baricitinib. Abemaciclib The excretion of Baricitinib can be decreased when combined with Abemaciclib. Aceclofenac Aceclofenac may decrease the excretion rate of Baricitinib which could result in a higher serum level. - Food Interactions
- Take with or without food. A high-fat meal can decrease the mean AUC and Cmax of baricitinib and delay Tmax, but not to a clinically singificant extent.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Baricitinib Tablet, film coated 4 mg/1 Oral Eli Lilly and Company 2021-12-20 Not applicable US 
Olumiant Tablet, film coated 4 mg/1 Oral Eli Lilly and Company 2022-05-10 Not applicable US Olumiant Tablet, film coated 4 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU 
Olumiant Tablet, film coated 1 mg/1 Oral Eli Lilly and Company 2019-10-08 Not applicable US Olumiant Tablet, film coated 4 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image OLUMIANT Baricitinib (2 mg) + Baricitinib (4 mg) Tablet, coated Oral ELI LILLY INTERAMERICA INC 2019-09-13 2024-09-30 Colombia 
OLUMIANT Baricitinib (2 mg) + Baricitinib (4 mg) Tablet, coated Oral ELI LILLY INTERAMERICA INC 2019-09-13 2024-09-30 Colombia
Categories
- ATC Codes
- L04AF02 — Baricitinib
- Drug Categories
- Amides
- Antineoplastic and Immunomodulating Agents
- Antirheumatic Agents
- Azetines
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Disease-modifying Antirheumatic Agents
- Drugs that are Mainly Renally Excreted
- Experimental Unapproved Treatments for COVID-19
- Heterocyclic Compounds, Fused-Ring
- Immunosuppressive Agents
- Janus Kinase Inhibitor
- Janus Kinase Inhibitors
- MATE 2 Inhibitors
- MATE 2 Substrates
- MATE 2 Substrates with a Narrow Therapeutic Index
- MATE inhibitors
- MATE substrates
- Narrow Therapeutic Index Drugs
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OAT3/SLC22A8 Substrates
- OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index
- OATP1B3 inhibitors
- OCT2 Inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Selective Immunosuppressants
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as pyrrolo[2,3-d]pyrimidines. These are aromatic heteropolycyclic compounds containing a pyrrolo[2,3-d]pyrimidine ring system, which is an pyrrolopyrimidine isomers having the 3 ring nitrogen atoms at the 1-, 5-, and 7-positions.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyrrolopyrimidines
- Sub Class
- Pyrrolo[2,3-d]pyrimidines
- Direct Parent
- Pyrrolo[2,3-d]pyrimidines
- Alternative Parents
- Pyrimidines and pyrimidine derivatives / Organosulfonamides / Organic sulfonamides / Sulfonyls / Pyrroles / Pyrazoles / Heteroaromatic compounds / Azetidines / Nitriles / Azacyclic compounds show 3 more
- Substituents
- Aromatic heteropolycyclic compound / Azacycle / Azetidine / Azole / Carbonitrile / Heteroaromatic compound / Hydrocarbon derivative / Nitrile / Organic nitrogen compound / Organic oxide show 13 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- ISP4442I3Y
- CAS number
- 1187594-09-7
- InChI Key
- XUZMWHLSFXCVMG-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)
- IUPAC Name
- 2-[1-(ethanesulfonyl)-3-(4-{7H-pyrrolo[2,3-d]pyrimidin-4-yl}-1H-pyrazol-1-yl)azetidin-3-yl]acetonitrile
- SMILES
- CCS(=O)(=O)N1CC(CC#N)(C1)N1C=C(C=N1)C1=C2C=CNC2=NC=N1
References
- Synthesis Reference
Mayence, A., & Vanden Eynde, J. J. (2019). Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. Pharmaceuticals (Basel, Switzerland), 12(1), 37. https://doi.org/10.3390/ph12010037
- General References
- Kuriya B, Cohen MD, Keystone E: Baricitinib in rheumatoid arthritis: evidence-to-date and clinical potential. Ther Adv Musculoskelet Dis. 2017 Feb;9(2):37-44. doi: 10.1177/1759720X16687481. Epub 2017 Jan 23. [Article]
- Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP, Macias WL, de Bono S, Schlichting DE, Smolen JS: Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247. [Article]
- O'Shea JJ, Kontzias A, Yamaoka K, Tanaka Y, Laurence A: Janus kinase inhibitors in autoimmune diseases. Ann Rheum Dis. 2013 Apr;72 Suppl 2:ii111-5. doi: 10.1136/annrheumdis-2012-202576. [Article]
- Markham A: Baricitinib: First Global Approval. Drugs. 2017 Apr;77(6):697-704. doi: 10.1007/s40265-017-0723-3. [Article]
- Mayence A, Vanden Eynde JJ: Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. Pharmaceuticals (Basel). 2019 Mar 12;12(1). pii: ph12010037. doi: 10.3390/ph12010037. [Article]
- Radi G, Simonetti O, Rizzetto G, Diotallevi F, Molinelli E, Offidani A: Baricitinib: The First Jak Inhibitor Approved in Europe for the Treatment of Moderate to Severe Atopic Dermatitis in Adult Patients. Healthcare (Basel). 2021 Nov 18;9(11). pii: healthcare9111575. doi: 10.3390/healthcare9111575. [Article]
- Ahmad A, Zaheer M, Balis FJ: Baricitinib . [Article]
- FDA: Emergency Use Authorization for Baricitinib in Combination with Remdesivir for COVID-19 [Link]
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Cayman Chemical: Baricitinib MSDS [Link]
- EMA Approved Drug Products: Olumiant (baricitinib) Oral Tablets [Link]
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use 2022 [Link]
- External Links
- KEGG Drug
- D10308
- PubChem Compound
- 44205240
- PubChem Substance
- 347828164
- ChemSpider
- 26373084
- BindingDB
- 50021656
- 2047232
- ChEBI
- 95341
- ChEMBL
- CHEMBL2105759
- ZINC
- ZINC000073069247
- PDBe Ligand
- 3JW
- Wikipedia
- Baricitinib
- PDB Entries
- 4w9x / 6vn8 / 6wto
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Recruiting Not Available Alopecia Areata (AA) / Janus Kinase Inhibitors 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Rheumatoid Arthritis 1 somestatus stop reason just information to hide 4 Completed Treatment Rheumatoid Arthritis 1 somestatus stop reason just information to hide 4 Recruiting Prevention Coronavirus Disease 2019 (COVID‑19) / Psoriatic Arthritis / Rheumatoid Arthritis / Spondylarthritis 1 somestatus stop reason just information to hide 4 Recruiting Treatment Atopic Dermatitis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 4 mg/1 Tablet Oral 2 mg Tablet Oral 2.000 mg Tablet Oral 4 mg Tablet, coated Oral Tablet, film coated Oral 1 mg/1 Tablet, film coated Oral 1 mg Tablet, film coated Oral 2 mg/1 Tablet, film coated Oral 2.000 mg Tablet, film coated Oral 4.000 mg Tablet, film coated Oral 2 mg Tablet, film coated Oral Tablet, film coated Oral 4 mg Tablet, coated Oral 2 mg Tablet, coated Oral 4 mg - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8420629 No 2013-04-16 2029-03-10 US US8158616 No 2012-04-17 2030-06-08 US US9089574 No 2015-07-28 2032-11-30 US US11045474 No 2021-06-29 2032-11-30 US US9737469 No 2017-08-22 2033-03-29 US US11806555 No 2011-11-02 2031-11-02 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source boiling point (°C) 707.2 MSDS - Predicted Properties
Property Value Source Water Solubility 0.357 mg/mL ALOGPS logP 1.08 ALOGPS logP -0.19 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 13.89 Chemaxon pKa (Strongest Basic) 3.91 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 120.56 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 105.55 m3·mol-1 Chemaxon Polarizability 36.72 Å3 Chemaxon Number of Rings 4 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 MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-8480f7e45a7a18750f2a Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00dj-3059000000-ce0c149784b49928c3db Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0009000000-0a4394ce2755d981bb82 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-1259000000-8cda5f38403581ec23e8 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0f79-0091000000-88e8b4aa9e4fcef80457 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0ika-6390000000-59591905479c29dbbabe 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]- 201.0770939 predictedDarkChem Lite v0.1.0 [M-H]- 177.21587 predictedDeepCCS 1.0 (2019) [M+H]+ 202.1073939 predictedDarkChem Lite v0.1.0 [M+H]+ 179.57387 predictedDeepCCS 1.0 (2019) [M+Na]+ 202.1282939 predictedDarkChem Lite v0.1.0 [M+Na]+ 186.8278 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In isolated enzyme assays, baricitinib inhibited the activities of JAK1 with IC50 value of 5.9nM.
- General Function
- Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:16239216, PubMed:28111307, PubMed:32750333, PubMed:7615558, PubMed:8232552). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:16239216, PubMed:32750333, PubMed:8232552)
- Specific Function
- Atp binding
- Gene Name
- JAK1
- Uniprot ID
- P23458
- Uniprot Name
- Tyrosine-protein kinase JAK1
- Molecular Weight
- 133275.995 Da
References
- Kuriya B, Cohen MD, Keystone E: Baricitinib in rheumatoid arthritis: evidence-to-date and clinical potential. Ther Adv Musculoskelet Dis. 2017 Feb;9(2):37-44. doi: 10.1177/1759720X16687481. Epub 2017 Jan 23. [Article]
- Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP, Macias WL, de Bono S, Schlichting DE, Smolen JS: Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247. [Article]
- Mayence A, Vanden Eynde JJ: Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. Pharmaceuticals (Basel). 2019 Mar 12;12(1). pii: ph12010037. doi: 10.3390/ph12010037. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In isolated enzyme assays, baricitinib inhibited the activities of JAK2 with IC50 value of 5.7nM.
- General Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins (PubMed:7615558, PubMed:9657743, PubMed:15690087). Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins (PubMed:9618263, PubMed:15690087). Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain (PubMed:9657743). Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. Part of a signaling cascade that is activated by increased cellular retinol and that leads to the activation of STAT5 (STAT5A or STAT5B) (PubMed:21368206). In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation (PubMed:20098430). Plays a role in cell cycle by phosphorylating CDKN1B (PubMed:21423214). Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin (PubMed:19783980)
- Specific Function
- Acetylcholine receptor binding
- Gene Name
- JAK2
- Uniprot ID
- O60674
- Uniprot Name
- Tyrosine-protein kinase JAK2
- Molecular Weight
- 130672.475 Da
References
- Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP, Macias WL, de Bono S, Schlichting DE, Smolen JS: Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016 Mar 31;374(13):1243-52. doi: 10.1056/NEJMoa1507247. [Article]
- Kuriya B, Cohen MD, Keystone E: Baricitinib in rheumatoid arthritis: evidence-to-date and clinical potential. Ther Adv Musculoskelet Dis. 2017 Feb;9(2):37-44. doi: 10.1177/1759720X16687481. Epub 2017 Jan 23. [Article]
- Mayence A, Vanden Eynde JJ: Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. Pharmaceuticals (Basel). 2019 Mar 12;12(1). pii: ph12010037. doi: 10.3390/ph12010037. [Article]
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- Curator comments
- In isolated enzyme assays, baricitinib inhibited the activities of JAK3 with IC50 value of >400nM.
- General Function
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta (IL2RB) and gamma chain (IL2RG) subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A and STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion
- Specific Function
- Atp binding
- Gene Name
- JAK3
- Uniprot ID
- P52333
- Uniprot Name
- Tyrosine-protein kinase JAK3
- Molecular Weight
- 125097.565 Da
References
- Mayence A, Vanden Eynde JJ: Baricitinib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Janus Kinases. Pharmaceuticals (Basel). 2019 Mar 12;12(1). pii: ph12010037. doi: 10.3390/ph12010037. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- In isolated enzyme assays, baricitinib inhibited the activities of TYK2 with IC50 value of 53nM.
- 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
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- In vitro, less than 10% of baricitinib is oxidatively metabolized by CYP3A4 [FDA Label].
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Coadministration of baricitinib with probenecid, a potent OAT3 inhibitor, resulted in increased AUC with no change in Cmax or Tmax of baricitinib. Concomitant use of OAT3 inhibitors such as diclofenac and ibupprofen may lead to increased exposure of baricitinib, however a clinically relevant interaction is not expected. Methotrexate, a substrate of several transporters including OAT3, is not reported to induce a clinically meaningful effect on baricitinib exposure. The inhibition was observed in vitro.
- General Function
- Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (PubMed:14586168, PubMed:15644426, PubMed:15846473, PubMed:16455804, PubMed:31553721). Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) (PubMed:14586168, PubMed:15846473, PubMed:15864504, PubMed:22108572, PubMed:23832370). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain (PubMed:11306713, PubMed:14586168, PubMed:15846473). E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange (PubMed:26377792). Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule (PubMed:11907186). Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate (PubMed:22108572, PubMed:23832370). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (PubMed:15644426). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (PubMed:11669456, PubMed:15846473, PubMed:16455804). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) (PubMed:14675047). May contribute to the release of cortisol in the adrenals (PubMed:15864504). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
- Specific Function
- Organic anion transmembrane transporter activity
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Organic anion transporter 3
- Molecular Weight
- 59855.585 Da
References
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Inhibition was observed 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: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Inhibition was observed in vitro, however, the FDA label states that this is unlikely to result in clinically significant drug interactions.
- General Function
- Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
- Specific Function
- Antiporter activity
- Gene Name
- SLC47A2
- Uniprot ID
- Q86VL8
- Uniprot Name
- Multidrug and toxin extrusion protein 2
- Molecular Weight
- 65083.915 Da
References
- Posada MM, Cannady EA, Payne CD, Zhang X, Bacon JA, Pak YA, Higgins JW, Shahri N, Hall SD, Hillgren KM: Prediction of Transporter-Mediated Drug-Drug Interactions for Baricitinib. Clin Transl Sci. 2017 Nov;10(6):509-519. doi: 10.1111/cts.12486. Epub 2017 Jul 27. [Article]
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Baracitinib FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition was observed in vitro.
- General Function
- Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651)
- Specific Function
- Alpha-ketoglutarate transmembrane transporter activity
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
References
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition was observed in vitro.
- 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:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:21128598, PubMed:9687576). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:15212162, PubMed:9260930, PubMed:9687576). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly 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 (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:16581093, PubMed:17460754, PubMed:9687576). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). 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). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373, PubMed:9260930). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine (PubMed:12538837, PubMed:21128598). Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (PubMed:11907186). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12395288, PubMed:16394027). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
- Specific Function
- Acetylcholine transmembrane transporter activity
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
References
- FDA Approved Drug Products: OLUMIANT (baricitinib) tablets, for oral use [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibition was observed in vitro.
- 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: OLUMIANT (baricitinib) tablets, for oral use [Link]
- 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: OLUMIANT (baricitinib) tablets, for oral use [Link]
Drug created at October 20, 2016 20:50 / Updated at January 03, 2023 04:10