Tofacitinib

Tofacitinib

Clinical data
Trade names	Xeljanz, Jakvinus
AHFS/Drugs.com	Xeljanz
License data	US FDA: Tofacitinib
Pregnancy category	US: C (Risk not ruled out)
Routes of administration	By mouth (tablets)
ATC code	L04AA29 (WHO)
Legal status
Legal status	US: ℞-only
Pharmacokinetic data
Bioavailability	74%
Protein binding	40%
Metabolism	Hepatic (via CYP3A4 and CYP2C19)
Biological half-life	3 hours
Excretion	Urine
Identifiers
IUPAC name 3-[(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile
Synonyms	CP-690550
CAS Number	477600-75-2
PubChem CID	9926791
IUPHAR/BPS	5677
DrugBank	DB08895 Y
ChemSpider	8102425
UNII	87LA6FU830
KEGG	D09970
ChEBI	CHEBI:71200 Y
ChEMBL	CHEMBL221959
ECHA InfoCard	100.215.928
Chemical and physical data
Formula	C16H20N6O
Molar mass	312.369 g/mol
3D model (Jmol)	Interactive image
SMILES CC2CCN(C(=O)CC#N)CC2N(C)c3ncnc1nccc13
InChI InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1 Key:UJLAWZDWDVHWOW-YPMHNXCESA-N InChI=1S/C16H20N6O/c1-11-5-8-22(14(23)3-6-17)9-13(11)21(2)16-12-4-7-18-15(12)19-10-20-16/h4,7,10-11,13H,3,5,8-9H2,1-2H3,(H,18,19,20)/t11-,13+/m1/s1 Key:UJLAWZDWDVHWOW-YPMHNXCESA-N

Tofacitinib (INN) is a drug of the janus kinase (JAK) inhibitor class, discovered and developed by the National Institutes of Health and Pfizer. Tofacitinib is marketed as Xeljanz and Jakvinus.

It is currently approved for the treatment of rheumatoid arthritis (RA) in the United States and other countries.

It has demonstrated effectiveness in the treatment of psoriasis in Phase 3 studies. It is being studied for treatment of inflammatory bowel disease, and other immunological diseases, as well as for the prevention of organ transplant rejection.

In November 2012, the U.S. FDA approved tofacitinib "to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response to, or who are intolerant of, methotrexate." It was later approved in Japan, Switzerland and others (but not the EU). It is marketed as Xeljanz in all regions except for Russia where it will be marketed as Jakvinus or Jaquinus.

It is an inhibitor of the enzyme janus kinase 1 (JAK1) and janus kinase 3 (JAK 3), which means that it interferes with the JAK-STAT signaling pathway, which transmits extracellular information into the cell nucleus, influencing DNA transcription.

In a mouse model of established arthritis, tofacitinib rapidly improved disease by inhibiting the production of inflammatory mediators and suppressing STAT1-dependent genes in joint tissue. This efficacy in this disease model correlated with the inhibition of both JAK1 and 3 signaling pathways, suggesting that tofacitinib may exert therapeutic benefit via pathways that are not exclusive to inhibition of JAK3.