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: Through the application of proprietary artificial intelligence (AI) algorithms baricitinib has been predicted to possess antiviral activity in addition to its known anti-inflammatory efficacy [1,8-9]. 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 (COVID-19 disease). In addition, the powerful anti-inflammatory activity of baricitinib (and potentially other approved JAK inhibitors such as fedratinib, and ruxolitinib) is likely to be effective against the pathological effects of raised cytokine levels (e.g. interferon γ) in patients with severe COVID-19. Short term use of baricitinib during the course of SARS-CoV-2 infection (7-14 days) is not anticipated to cause serious side-effects.
2D Structure
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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
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
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.
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).
External links