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
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. 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]
8. 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]
9. 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]
10. 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]