Baricitinib
[CAS# 1187594-09-7]

Identification

• Classification: Biochemical >> Inhibitor >> Tyrosine protein kinase/signal transducer and transcriptional activator inhibitor (JAK/STAT) >> JAK inhibitor
• Name: Baricitinib
• Synonyms: INCB 028050; LY 3009104; 1-(Ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-3-azetidineacetonitrile
• Molecular Formula: C₁₆H₁₇N₇O₂S
• Molecular Weight: 371.42
• CAS Registry Number: 1187594-09-7
• EC Number: 691-421-4
• SMILES: CCS(=O)(=O)N1CC(C1)(CC#N)N2C=C(C=N2)C3=C4C=CNC4=NC=N3

Properties

• Solubility: 74 mg/mL (DMSO), <1 mg/mL (water)
• Density: 1.56

Safety Data

• Hazard Symbols: GHS07;GHS08;GHS09 Danger
• Risk Statements: H302-H360-H373-H411
• Safety Statements: P203-P260-P264-P270-P273-P280-P301+P317-P318-P319-P330-P391-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - repeated exposure	STOT RE	2	H373
Reproductive toxicity	Repr.	1B	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Baricitinib, chemically known as (2-(1-(ethylsulfonyl)azetidine-3-methylene)-2-(4-(morpholinomethyl)phenyl)acetonitrile), is a novel small molecule inhibitor that targets Janus kinases (JAKs), specifically JAK1 and JAK2. Baricitinib was developed by Incyte Corporation and licensed to Eli Lilly and Company for further development and commercialization. It is designed as a selective inhibitor of JAK1 and JAK2, key enzymes involved in the signaling pathways of multiple cytokines, including interleukins and interferons. Baricitinib has a substituted azetidine ring and a phenylacetonitrile moiety, which are essential for its selective inhibition of JAK enzymes. Baricitinib is a white to off-white crystalline powder, usually taken orally in tablet form.

Baricitinib exerts its therapeutic effects by inhibiting JAK1 and JAK2, two substances involved in the intracellular signaling pathways of cytokines that play a role in inflammation and immune responses. By blocking these enzymes, baricitinib modulates the immune system's response and reduces inflammation associated with autoimmune diseases such as rheumatoid arthritis.

Baricitinib is primarily used to treat moderate to severe rheumatoid arthritis (RA) in adults who have not responded well to traditional DMARDs. It helps improve joint function, relieves pain, and inhibits structural damage caused by RA.

In addition to RA, baricitinib has also shown promising results in clinical trials for treating moderate to severe atopic dermatitis (eczema). It helps relieve the itching, redness, and inflammation associated with this chronic skin disease.

During the COVID-19 pandemic, baricitinib has gained attention for its potential role in controlling cytokine storms, a severe immune response seen in some COVID-19 patients. It is approved in combination with remdesivir for COVID-19 patients who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Common side effects of baricitinib include upper respiratory tract infections, nausea, and headaches. Serious adverse reactions may include increased risk of infection, thrombosis, and elevated liver enzymes. Regular monitoring of blood counts, liver enzymes, and lipid levels is recommended during treatment with baricitinib to manage potential risks.

References

2021. Safety of Baricitinib 4 mg for the Treatment of Moderate to Severe Rheumatoid Arthritis. Southern Medical Journal.
DOI: 10.14423/smj.0000000000001242

2021. Current jakinibs for the treatment of rheumatoid arthritis: a systematic review. Inflammopharmacology.
DOI: 10.1007/s10787-021-00822-x

2020. Baricitinib: Impact on Coronavirus Disease 2019 (COVID-19) Coagulopathy?. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
DOI: 10.1093/cid/ciaa1208