Tofacitinib

A summary of the most common chemical descriptors (InChI Key and SMILES codes) for Tofacitinib are summarized together with 3D and 2D structures and relevant physico-chemical properties.

What is the Tofacitinib?

The molecule Tofacitinib presents a molecular formula of C₁₆H₂₀N₆O and its IUPAC name is 3-[(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-3-oxopropanenitrile.

Tofacitinib (trade name: Xeljanz) is an immunosuppressive drug that belongs to the class of Janus kinase (JAK) inhibitors. It was approved by the U.S. Food and Drug Administration (FDA) in November 2012, for the treatment of adults with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to, or are intolerant of, methotrexate (MTX). It is the first JAK inhibitor to be approved for clinical use..

Tofacitinib works by inhibiting the activity of Janus kinase enzymes, which are involved in signaling pathways that regulate the function of immune cells. Inhibition of these enzymes leads to a reduction in the production of pro-inflammatory cytokines and other molecules that are involved in the pathogenesis of RA..

The efficacy of tofacitinib in the treatment of RA was demonstrated in two Phase III clinical trials, called ORAL Start and ORAL Standard. In the ORAL Start trial, tofacitinib was compared with placebo in patients who had not previously been treated with disease-modifying antirheumatic drugs (DMARDs). The ORAL Standard trial compared tofacitinib with adalimumab (Humira), an anti-tumor necrosis factor (TNF) biologic DMARD, in patients who had previously been treated with DMARDs including MTX..

In both trials, tofacitinib was associated with a significant reduction in the signs and symptoms of RA, as well as an improvement in physical function and quality of life. Tofacitinib was also associated with a reduction in the rate of progression of joint damage, as measured by x-ray..

The most common side effects of tofacitinib include upper respiratory tract infections, headache, diarrhea, and nasopharyngitis. Tofacitinib is associated with a small risk of serious infections, including tuberculosis and herpes zoster. It is also associated with a small risk of malignancies, including lymphoma..

Tofacitinib is a novel immunosuppressive drug that offers a new treatment option for patients with RA who have failed to respond to other DMARDs. Tofacitinib is generally well tolerated, with the most common side effects being mild to moderate in nature..

3D structure

Cartesian coordinates

Geometry of Tofacitinib in x, y and z coordinates (Å units) to copy/paste elsewhere. Generated with Open Babel software.

2D drawing

Molecule descriptors

Other names (synonyms)

IUPAC nomenclature provides a standardized method for naming chemical compounds. Although this system is widely used in chemistry, many chemical compounds have also other names commonly used in different contexts. These synonyms can come from a variety of sources and are used for a variety of purposes.

One common source of synonyms for chemical compounds is the common or trivial names, assigned on the basis of appearance, properties, or origin of the molecule.

Another source of synonyms are historical or obsolete names employed in the past, however replaced nowadays by more modern or standardized names.

In addition to common and historical names, chemical compounds may also have synonyms that are specific to a particular field or industry.

Reference codes for other databases

• CAS number (Chemical Abstracts Service Registry Number) is a unique identifier is assigned to every chemical compound indexed in the CAS database.
• Beilstein: The Beilstein database is a comprehensive source of information on organic chemistry, including information on chemical structures, properties, and reactions. The Beilstein database assigns unique identifiers which can be used to identify compounds in scientific literature and other sources.
• ChEBI (Chemical Entities of Biological Interest): ChEBI is a database of small chemical molecules that are of interest in the field of biology.
• PubChem CID (Compound Identifier): PubChem is a database of chemical compounds that is maintained by the National Institutes of Health (NIH).
• RTECS number (Registry of Toxic Effects of Chemical Substances): The RTECS is a database of information on the toxic effects of chemicals, including information on their structures and properties.
• ChEMBL (Compound Bioactivity Data): ChEMBL is a database of bioactivity data for small molecules, including information on their properties and structures.
• CompTox Dashboard (Environmental Protection Agency): The CompTox Dashboard is a database of information on the toxicology and environmental effects of chemicals.

Physico-Chemical properties

LogP and topological polar surface area (TPSA) values were estimated using Open Babel software.

The n-octanol/water partition coeficient (K_ow) data is applied in toxicology and drug research. K_ow values are used, to guess the environmental fate of persistent organic pollutants. High partition coefficients values, tend to accumulate in the fatty tissue of organisms. Molecules with a log(K_ow) (or LogP) greater than 5 are considered to bioaccumulate.

TPSA values are the sum of the surface area over all polar atoms or molecules, mainly oxygen and nitrogen, also including hydrogen atoms.

In medicinal chemistry, TPSA is used to assess the ability of a drug to permeabilise cells.

For molecules to penetrate the blood-brain barrier (and act on receptors in the central nervous system), TPSA values below 90 Ų are required. Thus, molecules with a polar surface area greater than 140 Ų tend to be poorly permeable to cell membranes.