Iloprost is a second generation structural analog of prostacyclin (PGI) with about ten-fold greater potency than the first generation stable analogs, such as carbaprostacyclin. Iloprost binds with equal affinity to human prostacyclin (Prostanoid IP) and prostaglandin EP1 receptors. Iloprost constricts the ilium and fundus circular smooth muscle as strongly as prostaglandin E2 (PGE2) itself. Iloprost inhibits the ADP, thrombin, and collagen-induced aggregation of human platelets. In whole animals, iloprost acts as a vasodilator, hypotensive, antidiuretic, and prolongs bleeding time. All of these properties help to antagonize the pathological changes that take place in the small pulmonary arteries of patients with pulmonary hypertension. Used for the treatment of pulmonary arterial hypertension.

Bortezomib is the therapeutic proteasome inhibitor. First, which is tested in humans. The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity. Bortezomib is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Bortezomib is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. Most commonly reported adverse reactions (incidence ≥30%) in clinical studies include asthenic conditions, diarrhea, nausea, constipation, peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, psychiatric disorders, anorexia and decreased appetite, neutropenia, neuralgia, leukopenia and anemia. Co-administration of ketoconazole, a potent CYP3A inhibitor, increased the exposure of bortezomib. Co-administration of melphalan-prednisone increased the exposure of bortezomib. However, this increase is unlikely to be clinically relevant.

Tadalafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Tadalafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with tadalafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, tadalafil should not cause an erection.Tadalafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by tadalafil enhances erectile function by increasing the amount of cGMP. Tadalafil is used for the treatment of erectile dysfunction.

Miglustat, an N-alkylated imino sugar, is a synthetic analogue of D-glucose. Miglustat is an inhibitor of the enzyme glucosylceramide synthase, which is a glucosyl transferase enzyme responsible for catalyzing the formation of glucosylceramide (glucocerebroside). Glucosylceramide is a substrate for the endogenous glucocerebrosidase, an enzyme that is deficient in Gaucher's disease. The accumulation of glucosylceramide due to the absence of glucocerebrosidase results in the storage of this material in the lysosomes of tissue macrophages, leading to widespread pathology due to infiltration of lipid-engorged macrophages in the viscera, lymph nodes, and bone marrow. This results in secondary hematologic consequences including sever anemia and thrombocytopenia, in addition to the characteristic progressive hepatosplenomegaly, as well as skeletal complications including osteonecrosis and osteopenia with secondary pathological fractures. Miglustat functions as a competitive and reversible inhibitor of the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions which results in the synthesis of most glycosphingolipids. The goal of treatment with miglustat is to reduce the rate of glycosphingolipid biosynthesis so that the amount of glycosphingolipid substrate is reduced to a level which allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy), reducing the accumulation of glucocerebroside in macrophages. In vitro and in vivo studies have shown that miglustat can reduce the synthesis of glucosylceramide-based glycosphingolipids. In clinical trials, miglustat improved liver and spleen volume, as well as hemoglobin concentration and platelet count. Inhibition of glycosphingolipid synthesis has also shown to reduce intracellular lipid storage, improve fluid-phase endosomal uptake and normalize lipid transport in peripheral blood B lymphocytes of NP-C patients, which results in a decrease in the potentially neurotoxic accumulation of gnagliosides GM2 and GM3, lactosylceramide and glucosylceramide, possibly preventing further neuronal damage. Other studies have also suggested that miglustat may indirectly modulate intracellular calcium homeostasis through its effects on glucosylceramide levels, and evidence has shown that an initiating factor in the pathogenesis of NP-C may be impaired calcium homeostasis related to sphingosine storage. Therefore, the effect that miglustat exerts on intracellular calcium levels may influence an important underlying pathogenic mechanism of NP-C. Miglustat is used for the treatment of adult patients with mild to moderate type 1 (nonneuropathic) Gaucher's disease for whom enzyme replacement therapy is not a therapeutic option (e.g. due to constraints such as allergy, hypersensitivity, or poor venous access). Now approved in some countries for the treatment of progressive neurological symptoms in adult and pediatric patients with Niemann-Pick disease type C (NP-C). Miglustat is marketed under the trade name Zavesca.

Sodium oxybate is the sodium salt of gamma-hydroxybutyrate (GHB), an endogenous metabolite of gamma-aminobutyric acid (GABA) a major inhibitory neurotransmitter. Evidence suggests a role for GHB as a neuromodulator/neurotransmitter. Under endogenous conditions and concentrations, and depending on the cell group affected, GHB may increase or decrease neuronal activity by inhibiting the release of neurotransmitters that are co-localised with GHB. After exogenous administration, most of the observed behavioural effects appear to be mediated via the activity of GHB at GABA(B) receptors, as long as the concentration is sufficient to elicit binding, which does not happen at endogenous concentrations. Xyrem (sodium oxybate) oral solution is indicated for the treatment of cataplexy in narcolepsy and excessive daytime sleepiness (EDS) in narcolepsy.

Imatinib (GLEEVEC®) is a tyrosine kinase inhibitor and antineoplastic agent that inhibits the BCR-ABL tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome abnormality in chronic myeloid leukaemia (CML). It inhibits proliferation and induces apoptosis in BCR-ABL positive cell lines as well as fresh leukemic cells from Philadelphia chromosome positive CML. Imatinib (GLEEVEC®) inhibits colony formation in assays using ex vivo peripheral blood and bone marrow samples from CML patients. It is also an inhibitor of the receptor tyrosine kinases for platelet-derived growth factor (PDGF) and stem cell factor (SCF), c-kit, and inhibits PDGF- and SCF-mediated cellular events. In vitro, imatinib (GLEEVEC®) inhibits proliferation and induces apoptosis in gastrointestinal stromal tumor (GIST) cells, which express an activating c-kit mutation.

Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol. The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. Mifepristone is used for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance and are not candidates for surgery or have had unsuccessful surgery.

NEO 212 is novel DNA alkylating agent exhibiting superior activity against breast cancer cells in vitro and intracranial triple-negative tumor growth in vivo. NEO212 is a conjugate of temozolomide (TMZ,) with the natural product perillyl alcohol (POH). NEO 212 causes DNA damage and cell death much more efficiently than TMZ because linkage with POH increased it's biological half-life and thus provided greater opportunity for placement of cytotoxic DNA lesions.

Armodafinil is the R-enantiomer of modafinil, a wake-promoting agent, that primarily affects areas of the brain involved in controlling wakefulness. Armodafinil is an indirect dopamine receptor agonist; both armodafinil and modafinil bind in vitro to the dopamine transporter and inhibit dopamine reuptake. Armodafinil tablets are indicated to improve wakefulness in adult patients with excessive sleepiness associated with obstructive sleep apnea (OSA), narcolepsy, or shift work disorder (SWD). Once-daily armodafinil was generally well tolerated in adult patients with excessive sleepiness associated with OSA (despite treatment of the underlying condition), narcolepsy or SWSD.

Nelfinavir is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Nelfinavir binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs. Nelfinavir inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles. Nelfinavir is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. Nelfinavir is marketed under the brand name Viracept.