Enzyme Modulators

Zileuton is an inhibitor of the 5-lipoxygenase enzyme, thus preventing the leukotrienes LTE4, LDT4, LTB4 and LTC4 from being formed. This in turn reduces inflammation, bronchoconstriction and mucus secretion in the airways. As a result, Zileuton can be used in the treatment and management of asthma and allergic rhinitis. Studies have shown that Zileuton has the potential to reverse dementia-related brain damage.

A cytidine analogue and inhibitor of DNA methyl transferases (DNMTs) with anti-cancer activity. This stable, hydrophilic compound forms covalent complexes between DNMT and zebularine-substrate DNA. It causes DNA lesions that block replication and cause replication fork collapse, leading to the formation of DNA double-strand breaks. It was also shown that zebularine-induced DNA methylation decrease in the IL-1β promoter region and disrupts molecular mechanisms of neuroinflammation. Moreover, this molecule down-regulates the DNA-methylation profile in the pluripotency genes’ promoters, which leads to improved development of somatic cell nuclear transfer (SCNT) embryos.

EGFR tyrosine kinase inhibitor; pro-apoptotic; antiproliferative in cancer cells

Apremilast is the commercial name of a phosphodiesterase-4 (PDE4) inhibitor developed to treat chronic inflammatory disorders. Similarly to thalidomide, the apremilast molecule carries a phthalimide ring, but it lacks however the glutarimide ring needed to bind to cereblon, specifically targeted by thalidomide. As a drug, apremilast is indicated for the treatment of psoriasis and psoriatic arthritis.

Inhibitor of MEK1 and MEK2 kinases

Thymidylate synthase inhibitor

Inhibitor of EIF2AK3/PERK kinases

Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) which is used to treat various types of pain and inflammation caused by arthritis. It is also a COX-2 inhibitor which reduces gastrointestinal effects of this drug. Inhibiting these enzymes, allow for a decrease in inflammatory symptoms.

Immune suppressant; prevents pro-inflammatory cytokine release

Analeptic

Pan-tyrosine kinase inhibitor (VEGFR2, c-MET, RET, KIT); anti-neoplastic

Inhibitor of dioxygenase IDO1

A 939572 is an inhibitor of stearoyl-CoA desaturase 1 (SCD1). It exhibits anticancer activity as it inhibits cell growth and promotes cell death in human non-small cell lung carcinoma cells.

Atorvastatin is an HMG-CoA reductase inhibitor which is used to lower lipid levels and to reduce the risk of cardiovascular disease. This drug belongs to the class of medicines called statins. It lowers abnormal levels of cholesterol and lipids to reduce the risk of cardiovascular disease by inhibiting the enzyme HMG-CoA.

Inhibitor of COX-2 and PDE4 enzymes; NSAID of coxib class

6-Thioguanine is a purine analog used in the therapy for leukemia and for remission consolidation in patients with acute nonlymphocytic anemia. This drug also has antimetabolite action. It replaces guanine during DNA replication. This substitution disrupts the accurate pairing of DNA bases, leading to errors in DNA replication and hinders cell division.

Selective inhibitor of the Src kinase family with subnanomolar IC50 values and good selectivity over c-Abl, PDGFRα and c-Kit kinases. The compound is effective in inhibiting growth in drug resistant cancer cell lines. In a recent study, it inhibited the growth of HER2-positive breast cancer cell lines which were resistant to pan-HER family kinase inhibitors such as lapatinib.