Teriflunomide is the active metabolite

Active metabolite

- Prodrugs :Sometimes drugs are formulated deliberately so they will break down inside the body to form the active drug, these are called prodrugs. The reason for this may be because the drug is more stable during manufacture and storage as the prodrug form, or because the prodrug is better...

 of leflunomide

Leflunomide

Leflunomide is a medication of the DMARD type, used in active moderate to severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor.-Basic chemical, pharmacological, and marketing data:...

. Teriflunomide was investigated in the Phase III clinical trial TEMSO as a medication for multiple sclerosis

Multiple sclerosis

Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...

 (MS). The study was completed in July 2010. 2-year results were positive.

Mechanisms of action

Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis

De novo synthesis

De novo synthesis refers to the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to their being recycled after partial degradation. For example, nucleotides are not needed in the diet as they can be constructed from small precursor molecules such as...

 by blocking the enzyme dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase

Dihydroorotate dehydrogenase is an enzyme that catalyzes the fourth step in the de novo biosynthesis of pyrimidine. It converts dihydroorotate to orotate:...

.
It is uncertain whether this explains its effect on MS lesions.

Teriflunomide inhibits rapidly dividing cells, including activated T cells, which are thought to drive the disease process in MS. Teriflunomide may decrease the risk of infections compared to chemotherapy-like drugs because of its more-limited effects on the immune system.

It has been found that teriflunomid blocks the transcription factor NF-κB. It also inhibits tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....

 enzymes, but only in high doses not clinically used.

Activation of leflunomide to teriflunomide

→↔

The structure which results from ring opening can interconvert between the E and Z

E-Z notation

E-Z notation, or the E-Z convention, is the IUPAC preferred method of describing the stereochemistry of double bonds in organic chemistry...

 enol

Enol

Enols are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. Deprotonated anions of enols are called enolates...

ic forms (and the corresponding keto-amide), with the Z enol being the most stable and therefore most predominant form.

See also

See Leflunomide

Leflunomide

Leflunomide is a medication of the DMARD type, used in active moderate to severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor.-Basic chemical, pharmacological, and marketing data:...

for information on pharmacokinetics, side-effects, contraindications and other data.