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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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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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
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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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)
InChI Key XUZMWHLSFXCVMG-UHFFFAOYSA-N
References
1. ACS. 
Molecule of the Week Archive- Baricitinib.
Accessed on 10/03/2020. Modified on 10/03/2020. ACS, https://www.acs.org/content/acs/en/molecule-of-the-week/archive/b/baricitinib.html
2. Clark JD, Flanagan ME, Telliez JB. (2014)
Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.
J Med Chem, 57 (12): 5023-38. [PMID:24417533]
3. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF et al.. (2010)
Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.
J Immunol, 184 (9): 5298-307. [PMID:20363976]
4. Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP et al.. (2016)
Baricitinib in Patients with Refractory Rheumatoid Arthritis.
N Engl J Med, 374 (13): 1243-52. [PMID:27028914]
5. Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, Sanchez GA, Goldbach-Mansky R, Christiano AM, Clynes R et al.. (2015)
Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.
EBioMedicine, 2 (4): 351-5. [PMID:26137574]
6. Kennedy Crispin M, Ko JM, Craiglow BG, Li S, Shankar G, Urban JR, Chen JC, Cerise JE, Jabbari A, Winge MC et al.. (2016)
Safety and efficacy of the JAK inhibitor tofacitinib citrate in patients with alopecia areata.
JCI Insight, 1 (15): e89776. [PMID:27699252]
7. King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, Hordinsky M, Dutronc Y, Wu WS, McCollam J et al.. (2022)
Two Phase 3 Trials of Baricitinib for Alopecia Areata.
N Engl J Med, 386 (18): 1687-1699. [PMID:35334197]
8. Mackay-Wiggan J, Jabbari A, Nguyen N, Cerise JE, Clark C, Ulerio G, Furniss M, Vaughan R, Christiano AM, Clynes R. (2016)
Oral ruxolitinib induces hair regrowth in patients with moderate-to-severe alopecia areata.
JCI Insight, 1 (15): e89790. [PMID:27699253]
9. Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Stebbing J. (2020)
Baricitinib as potential treatment for 2019-nCoV acute respiratory disease.
Lancet, 395 (10223): e30-e31. DOI: 10.1016/S0140-6736(20)30304-4 [PMID:32032529]
10. Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P. (2020)
COVID-19: combining antiviral and anti-inflammatory treatments.
Lancet Infect Dis, 20 (4): 400-402. [PMID:32113509]
11. Waibel M, Thomas HE, Wentworth JM, Couper JJ, MacIsaac RJ, Cameron FJ, So M, Krishnamurthy B, Doyle MC, Kay TW. (2022)
Investigating the efficacy of baricitinib in new onset type 1 diabetes mellitus (BANDIT)-study protocol for a phase 2, randomized, placebo controlled trial.
Trials, 23 (1): 433. [PMID:35606820]
12. Waibel M, Wentworth JM, So M, Couper JJ, Cameron FJ, MacIsaac RJ, Atlas G, Gorelik A, Litwak S, Sanz-Villanueva L et al.. (2023)
Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes.
N Engl J Med, 389 (23): 2140-2150. [PMID:38055252]
13. Xing L, Dai Z, Jabbari A, Cerise JE, Higgins CA, Gong W, de Jong A, Harel S, DeStefano GM, Rothman L et al.. (2014)
Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.
Nat Med, 20 (9): 1043-9. [PMID:25129481]