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)
Bioactivity Comments
Preclinical studies of baricitinib have shown it to be effective in rat models of rheumatoid arthritis [3].
A single patient with alopecia areata (AA) with comorbid CANDLE syndrome (a immunoproteasome-related disorder with a prominent interferon (IFN) signature, a disease feature shared with AA), recruited to a clinical trial testing baricitinib as a treatment for their CANDLE syndrome (NCT01724580) experienced significant hair regrowth [5]. Mechanistic assessment in a mouse AA model, confirmed that clinical improvement correlated with baricitinib-induced resolution of the IFN signature. Other JAK inhibitors such as tofacitinib and ruxolitinib have also been reported to promote hair regrowth in AA in early stage trials [6,8,13].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
AP2 associated kinase 1 Hs Inhibitor Inhibition 7.8 pKd - 10
pKd 7.8 (Kd 1.7x10-8 M) [10]
Description: Binding affinity determined in a cell-free biochemical assay.
BMP2 inducible kinase Hs Inhibitor Inhibition 7.4 pKd - 10
pKd 7.4 (Kd 4x10-8 M) [10]
Description: Binding affinity determined in a cell-free biochemical assay.
cyclin G associated kinase Hs Inhibitor Inhibition 6.9 pKd - 10
pKd 6.9 (Kd 1.36x10-7 M) [10]
Description: Binding affinity determined in a cell-free biochemical assay.
Janus kinase 1 Primary target of this compound Hs Inhibitor Inhibition 8.2 – 8.4 pIC50 - 2-3
pIC50 8.4 (IC50 4x10-9 M) [2]
pIC50 8.2 (IC50 5.9x10-9 M) [3]
Janus kinase 2 Primary target of this compound Hs Inhibitor Inhibition 8.1 – 8.2 pIC50 - 2-3
pIC50 8.2 (IC50 5.7x10-9 M) [3]
pIC50 8.1 (IC50 7x10-9 M) [2]
tyrosine kinase 2 Hs Inhibitor Inhibition 7.2 pIC50 - 2
pIC50 7.2 (IC50 6.1x10-8 M) [2]
Janus kinase 3 Hs Inhibitor Inhibition 6.1 pIC50 - 2
pIC50 6.1 (IC50 7.87x10-7 M) [2]