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
- Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
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.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. Acemetacin Acemetacin may decrease the excretion rate of Baricitinib which could result in a higher serum level. Acetaminophen Acetaminophen may decrease the excretion rate of Baricitinib which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Baricitinib which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid The serum concentration of Baricitinib can be increased when it is combined with Acetylsalicylic acid. Aclidinium Aclidinium may decrease the excretion rate of Baricitinib which could result in a higher serum level. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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 Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU 
Olumiant Tablet, film coated 4 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Olumiant Tablet, film coated 2 mg/1 Oral Eli Lilly and Company 2018-05-31 Not applicable US Olumiant Tablet, film coated 2 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Olumiant Tablet, film coated 4 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Olumiant Tablet, film coated 2 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Olumiant Tablet, film coated 4 mg Oral Eli Lilly Nederland B.V. 2020-12-16 Not applicable EU Olumiant Tablet 2 mg Oral Eli Lilly & Co. Ltd. 2018-09-27 Not applicable Canada 
Olumiant Tablet, film coated 2 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
- L04AA37 — 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
Phase Status Purpose Conditions Count 4 Active Not Recruiting Treatment Rheumatoid Arthritis 1 4 Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) 1 4 Recruiting Treatment Rheumatoid Arthritis 2 4 Recruiting Treatment Systemic; Sclerosis, Progressive 1 3 Active Not Recruiting Other Bone Mineral Density / Finger Joints / Rheumatoid Arthritis 1 3 Active Not Recruiting Treatment Alopecia Areata (AA) 1 3 Active Not Recruiting Treatment Atopic Dermatitis 3 3 Completed Treatment Atopic Dermatitis 4 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 3 3 Completed Treatment Juvenile Idiopathic Arthritis (JIA) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral 4 mg/1 Tablet Oral 2 mg Tablet, coated Oral Tablet, film coated Oral 1 mg/1 Tablet, film coated Oral 2 mg/1 Tablet, film coated Oral Tablet, film coated Oral 2.000 mg Tablet, film coated Oral 4.000 mg Tablet, film coated Oral 2 MG 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
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 Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Targets
- 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
- Ubiquitin protein ligase binding
- Specific Function
- Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway. Kinase partner for the interleukin (IL)-2 receptor.
- 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
- Sh2 domain binding
- Specific 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 adaptiv...
- 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
- Protein tyrosine kinase activity
- Specific 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...
- 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
- Protein tyrosine kinase activity
- Specific Function
- Probably involved in intracellular signal transduction by being involved in the initiation of type I IFN signaling. Phosphorylates the interferon-alpha/beta receptor alpha chain.
- 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
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- 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
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- 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
- Xenobiotic-transporting atpase activity
- Specific Function
- High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
- Gene Name
- ABCG2
- Uniprot ID
- Q9UNQ0
- Uniprot Name
- ATP-binding cassette sub-family G member 2
- 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
- Drug transmembrane transporter activity
- Specific Function
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
- 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
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- 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
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- 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
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- 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
- Xenobiotic-transporting atpase activity
- Specific Function
- Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
- Gene Name
- ABCB1
- Uniprot ID
- P08183
- Uniprot Name
- Multidrug resistance protein 1
- 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 June 27, 2022 14:55