Pirfenidone is a synthetic antifibrotic agent indicated for the treatment of idiopathic pulmonary fibrosis as Esbriet. Pirfenidone inhibits fibroblast, epidermal, platelet-derived, and transforming beta-1 growth factors. It also inhibits DNA synthesis and the production of mRNA for collagen types I and III, resulting in a reduction in radiation-induced fibrosis. Pirfenidone has demonstrated activity in multiple fibrotic conditions however the exact mechanism of action of pirfenidone in the treatment of IPF has not been established.

Nintedanib is a receptor tyrosine kinase inhibitor with potential antiangiogenic and antineoplastic activities. It is the only kinase inhibitor drug approved to treat idiopathic pulmonary fibrosis. that targets multiple receptor tyrosine kinases (RTKs) and non-receptor tyrosine kinases (nRTKs). Nintedanib inhibits the following RTKs: platelet-derived growth factor receptor (PDGFR) α and β, fibroblast growth factor receptor (FGFR) 1-3, vascular endothelial growth factor receptor (VEGFR) 1-3, and Fms-like tyrosine kinase-3 (FLT3). Among them, FGFR, PDGFR, and VEGFR have been implicated in IPF pathogenesis. Nintedanib binds competitively to the adenosine triphosphate (ATP) binding pocket of these receptors and blocks the intracellular signaling which is crucial for the proliferation, migration, and transformation of fibroblasts representing essential mechanisms of the IPF pathology.

Suvorexant is a selective dual antagonist of orexin receptors OX1R and OX2R. It has been approved for the treatment of insomnia. The mechanism by which suvorexant exerts its therapeutic effect in insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.

Tasimelteon, developed by Vanda Pharmaceuticals Inc under license from Bristol-Myers Squibb Co, is a melatonin receptor agonist. Tasimelteon differs structurally from melatonin and drugs with known melatonin agonist activity, in particular by its distinct aromatic group and linker. Tasimelteon bears also no structural relationship to any other approved active substance. Tasimelteon is presumably acts through activation of MT1 and MT2 G-protein coupled receptors, which are involved primarily in inhibition of neuronal firing and phase shift of circadian rhythms. Tasimelteon is approved for the treatment of Non24-Hour Sleep-Wake Disorder.

Apremilast (brand name Otezla) selective inhibitor of phosphodiesterase 4 is used for the treatment of patients with moderate to severe plaque psoriasis. OTEZLA is the first and only PDE4 inhibitor approved for the treatment of plaque psoriasis, a chronic inflammatory disease of the skin resulting from an uncontrolled immune response. Apremilast also inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It has anti-inflammatory activity. By inhibiting PDE-4, apremilast increases intracellular levels of cAMP and thereby inhibits the production of multiple proinflammatory mediators including PDE-4, TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase.

Macitentan is an orally active, dual endothelin receptor antagonist with tissue targeting properties. Macitentan inhibits both ETA and ETB receptors and prevents them from binding to ET-1. Macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells. One of the metabolites of macitentan is also pharmacologically active at the ET receptors and is estimated to be about 20% as potent as the parent drug in vitro. Macitentan is approved in the EU (as monotherapy or combination therapy) for the long-term treatment of pulmonary arterial hypertension (PAH) in adults of WHO functional class II or III, and in the USA for the treatment of PAH (WHO group I) to delay disease progression and reduce hospitalization for PAH.

Vortioxetine is an antidepressant for the treatment of major depressive disorder. Vortioxetine’s mechanism of action is not fully understood. Vortioxetine binds with high affinity to the serotonin transporter and its antidepressant actions are believed to be secondary to enhancing serotonin in the central nervous system through inhibition of reuptake. Vortioxetine also displays binding affinities to other serotonin (5-HT) receptors, including 5-HT3, 5-HT1A, and 5-HT7. Due to multimodal neurotransmitter enhancer profile, it has been suggested that it might need lesser receptor occupancy rate for clinical trials than other selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors. Since vortioxetine is an agonist and antagonist of multiple serotonin receptors, potential interactions may occur with other medications that alter the serotonergic pathways. There is an increased risk of serotonin syndrome when vortioxetine is used in combination with other serotonergic agents.

Dabrafenib is a selective, orally bioavailable inhibitor of Mutant BRAF protein kinase with potential antineoplastic activity. Dabrafenib inhibits BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM. BRAF belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. Mutations in BRAF are associated with increased growth and proliferation of cancer cells. By inhibiting BRAF kinase dabrafenib negatively regulates the proliferation of tumor cells which contain a mutated BRAF gene. Dabrafenib (in combination with trametinib or alone) is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation

Vilanterol (INN, USAN) is an ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA), which was approved in May 2013 in combination with fluticasone furoate for sale as Breo Ellipta by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease (COPD). Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs. Vilanterol is available in following combinations: a) with inhaled corticosteroid fluticasone furoate — fluticasone furoate/vilanterol (trade names Breo Ellipta , Relvar Ellipta; b) with muscarinic antagonist umeclidinium bromide — umeclidinium bromide/vilanterol (trade name Anoro Ellipta).

Dimethyl fumarate (DMF) is the methyl ester of fumaric acid. DMF was initially recognized as a very effective hypoxic cell radiosensitizer. Later, DMF combined with three other fumaric acid esters (FAE) was licensed in Germany as oral therapy for psoriasis (trade name Fumaderm). Phase III clinical trials found that DMF (BG-12) successfully reduced relapse rate and increased time to progression of disability in multiple sclerosis (trade name Tecfidera). DMF is thought to have immunomodulatory properties without significant immunosuppression. The mechanism of action of dimethyl fumarate in multiple sclerosis is not well understood. It is thought to involve dimethyl fumarate degradation to its active metabolite monomethyl fumarate (MMF) then MMF up-regulates the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway that is activated in response to oxidative stress. Dimethyl fumarate is marketed under the brand name Tecfidera.