baricitinib

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Ligands
baricitinib

GtoPdb Ligand ID: 7792

Synonyms: INCB-028050 | INCB028050 | LY-3009104 | LY3009104 | Olumiant®

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.

View interactive charts of activity data across species

2D Structure

Physico-chemical Properties

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

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

SMILES / InChI / InChIKey

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)
InChI Key	XUZMWHLSFXCVMG-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

No information available.

No information available.

Summary of Clinical Use
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].

Summary of Clinical Use

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
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.

Mechanism Of Action and Pharmacodynamic Effects

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