baricitinib   Click here for help

GtoPdb Ligand ID: 7792

Synonyms: INCB-028050 | INCB028050 | LY-3009104 | LY3009104 | Olumiant®
Approved drug PDB Ligand Immunopharmacology Ligand
baricitinib is an approved drug (EMA (2017), FDA (2018))
Compound class: Synthetic organic
Comment: Baricitinib is a JAK1 and 2 selective inhibitor. The compound is orally bioavailable.

SARS-CoV-2 and COVID-19: The powerful anti-inflammatory activity of baricitinib (and potentially other approved JAK inhibitors such as fedratinib, and ruxolitinib) was suggested as potential therapeutic option to combat the immunopathological effects of SARS-CoV-2 infection in patients with severe COVID-19. A number of small-medium sized clinical studies have examined the effect of short-term baricitinib (or other JAK inhibitors) treatment in hospitalised patients with confirmed COVID-19. Such short term use of this drug during the course of SARS-CoV-2 infection (7-14 days) is not anticipated to cause serious side-effects. In March 2022, data reported from the largest of the baricitinib studies (part of the University of Oxford-led RECOVERY trial) indicated that it provided clinical benefit in hospitalised COVID-19 patients, including in those already receiving other standard care immunomodulatory treatments (e.g. dexamethasone, tocilizumab) or the antiviral drug remdesivir. This made baricitinib the 4th effective COVID-19 therapy to be identified by the RECOVERY trial.

Through the application of proprietary artificial intelligence (AI) algorithms baricitinib was predicted to possess antiviral activity in addition to its known anti-inflammatory efficacy [1,9-10]. Antiviral activity is predicted to arise from inhibition of the numb-associated kinase (NAK) AAK1 which is an important regulator of clathrin-mediated endocytosis. Inhibition of AAK1 would likely reduce the ability of viruses to infect lung cells, and is being proposed as a pharmacological mechanism that warrants further investigation as a treatment for SARS-CoV-2 infection.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 128.94
Molecular weight 371.12
XLogP 0.41
No. Lipinski's rules broken 0
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Canonical SMILES N#CCC1(CN(C1)S(=O)(=O)CC)n1ncc(c1)c1ncnc2c1cc[nH]2
Isomeric SMILES N#CCC1(CN(C1)S(=O)(=O)CC)n1ncc(c1)c1ncnc2c1cc[nH]2
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)
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Summary of Clinical Use Click here for help
The EMA granted baricitinib marketing authorisation in February 2017, for the treatment of rheumatoid arthritis (RA). This approval covered doses of either 2 or 4 mg. Phase 3 trial results reporting significant clinical improvement in patients who's symptoms had failed to respond to other disease-modifying antirheumatic drugs (DMARDs) were published in [4]. These are the results of the RA-BEACON study NCT01721044. FDA approval, as a once daily treatment for moderately-to-severely active RA, in patients with an inadequate response to one or more tumour necrosis factor (TNF) inhibitor therapies, was granted in June 2018, but only for the 2 mg dose. In both jurisdictions, baricitinib can be used as monotherapy, or in combination with methotrexate or other non-biologic DMARDs. Use of baricitinib in combination with other JAK inhibitors, biologic DMARDs, or with potent immunosuppressants such as azathioprine and cyclosporin A is not recommended.
Baricitinib was approved by the FDA as the first systemic, once-daily therapy for severe alopecia areata in June 2022.

SARS-CoV-2 and COVID-19: In November 2020, the FDA granted the combination of baricitinib + remdesivir emergency use authorisation (EUA) as a treatment option for hospitalised COVID-19 patients, based on data from the ACTT-2 study (NCT04401579).

Most recently (late 2023), baricitinib has been shown to preserve β-cell function in patients with new-onset Type 1 diabetes [12].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Baricitinib inhibits the intracellular signalling that is induced by multiple proinflammatory cytokines, including IL-6 and IL-23, and this action evokes an improvement in clinical measures of autoinflammatory diseases.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01721044 A Moderate to Severe Rheumatoid Arthritis Study Phase 3 Interventional Eli Lilly and Company
NCT04401579 Adaptive COVID-19 Treatment Trial 2 (ACTT-2) Phase 3 Interventional National Institute of Allergy and Infectious Diseases (NIAID) The combination of baricitinib plus vs. remdesivir alone is being evaluated in the Adaptive COVID-19 Treatment Trial 2 (ACTT-2) study, which began in May 2020. In mid September 2020 baricitinib's manufacturer Eli Lilly published a press release that claimed that the drug combination decreased median recovery time across all (hospitalised) COVID-19 patients treated, by one day, compared to remdesivir monotherapy (access the press release here).
NCT03899259 A Study of Baricitinib (LY3009104) in Adults With Severe or Very Severe Alopecia Areata Phase 3 Interventional Eli Lilly and Company This is also known as the BRAVE-AA2 study 7
NCT03570749 A Study of Baricitinib (LY3009104) in Participants With Severe or Very Severe Alopecia Areata Phase 2/Phase 3 Interventional Eli Lilly and Company This is also known as the BRAVE-AA1 study. In this study and the BRAVE-AA2 study, oral baricitinib was superior to placebo in promoting hair regrowth in patients with severe alopecia areata. 7
NCT04774224 Baricitinib in New-onset Type 1 Diabetes Phase 2 Interventional St Vincent's Institute of Medical Research 11
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