Cholic acid is a primary bile acid synthesized from cholesterol in the liver. Endogenous bile acids including cholic acid enhance bile flow and provide the physiologic feedback inhibition of bile acid synthesis. The mechanism of action of cholic acid has not been fully established; however, it is known that cholic acid and its conjugates are endogenous ligands of the nuclear receptor, farnesoid X receptor (FXR). FXR regulates enzymes and transporters that are involved in bile acid synthesis and in the enterohepatic circulation to maintain bile acid homeostasis under normal physiologic conditions. U.S. Food and Drug Administration approved Cholbam (cholic acid) capsules, the first FDA approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders).

Miltefosine is an anti-leishmanial agent. It is an alkyl phospholipids compound, was originally intended for breast cancer and other solid tumors. However, it could not be developed as an oral agent because of dose-limiting gastro-intestinal toxicity, and only a topical formulation is approved for skin metastasis. But Miltefosine showed excellent antileishmanial activity both in vitro and in experimental models. Miltefosine is effective in vitro against both promastigotes and amastigotes of various species of Leishmania and also other kinetoplastidae (Trypanosoma cruzi,T. brucei) and other protozoan parasites (Entamoeba histolytica, Acanthamoeba). Mechanism of action is unknown. It is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome c oxidase (mitochondrial function), and apoptosis-like cell death. Miltefosine is approved for the treatment of Visceral leishmaniasis (due to Leishmania donovani), Cutaneous leishmaniasis (due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis) and Mucosal leishmaniasis (due to Leishmania braziliensis).

Dehydroepiandrosterone (INTRAROSA™, prasterone) is a major C19 steroid produced from cholesterol by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (INTRAROSA, prasterone) is structurally similar to, and is a precursor of, androstenedione, testosterone, estradiol, estrone and estrogen. It indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. The mechanism of action of dehydroepiandrosterone (INTRAROSA, prasterone) in postmenopausal women with vulvar and vaginal atrophy is not fully established.

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.

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.

Belinostat is a hydroxamate-type histone deacetylase inhibitor indicated for the treatment of relapsed or refractory peripheal T-cell lymphoma. The compound received orphan drug designation for the treatment of malignant thymomas. Acting on a histone deacetylase Belinostat causes the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase. PXD101 has been shown in preclinical studies to have the potential to treat a wide range of solid and hematologic malignancies either as a monotherapy or in combination with other active agents, and both an oral and intravenous formulation of the drug are being evaluated in clinical trials.

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.

Ibrutinib is an orally bioavailable Bruton's tyrosine kinase (BTK) inhibitor indicated for the treatment of mantle cell lymphoma (MCL) patients that previously received at least one therapy. The drug was jointly developed by Janssen Biotech and Pharmacyclics. Ibrutinib selectively binds to Cys-481 residue in the allosteric inhibitory segment of BTK (TK/SH1 domain), and irreversibly blocks its enzymatic activity thus preventing B-cell activation and signaling, totally blocking the B-cell receptor and cytokine receptor pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. Apart from mantle cell lymphoma Ibrutinib is approved for the treatment of chronic lymphocytic leukemia and Waldenstrom Macroglobulinemia.