Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor. Sunitinib was evaluated for its inhibitory activity against a variety of kinases and was identified as an inhibitor of platelet-derived growth factor receptors (PDGFRa and PDGFRb), vascular endothelial growth factor receptors (VEGFR1, VEGFR2, and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine kinase-3 (FLT3), colony-stimulating factor receptor Type 1 (CSF-1R), and the glial cell-line derived neurotrophic factor receptor (RET). Sunitinib adverse events are considered somewhat manageable and the incidence of serious adverse events low. The most common adverse events associated with sunitinib therapy are fatigue, diarrhea, nausea, anorexia, hypertension, yellow skin discoloration, hand-foot skin reaction, and stomatitis. In the placebo-controlled Phase III GIST study, adverse events which occurred more often with sunitinib than placebo included diarrhea, anorexia, skin discoloration, mucositis/stomatitis, asthenia, altered taste, and constipation. Dose reductions were required in 50% of the patients studied in RCC in order to manage the significant toxicities of this agent.

Dasatinib [BMS 354825] is an orally active, small molecule, dual inhibitor of both SRC and ABL kinases that is under development with Bristol-Myers Squibb for the treatment of patients with chronic myelogenous leukaemia (CML) and imatinib-acquired resistance/intolerance. It’s used for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia with resistance or intolerance to prior therapy. Also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. While imatinib remains a frontline therapy for CML, patients with advanced disease frequently develop resistance to imatinib therapy through multiple mechanisms. Dasatinib is also undergoing preclinical evaluation for its potential as a therapy against multiple myeloma. Bristol-Myers Squibb has a composition-of-matter patent covering this research approach that will expire in 2020. Dasatinib, at nanomolar concentrations, inhibits the following kinases: BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-KIT, EPHA2, and PDGFRβ. Based on modeling studies, dasatinib is predicted to bind to multiple conformations of the ABL kinase.

Ciclesonide is a glucocorticoid receptor agonist indicated for the treatment of allergic rhinitis (Omnaris nasal spray) and asthma (Alvesco). It was also developed by Byk Gulden for chronic obstructive pulmonary disease (COPD), but no development had been reported for this indication since 1999. Ciclesonide is a pro-drug and rapidly metabolized to C21-desisobutyryl-ciclesonide which is more potent toward GR receptor than the parent drug.

Rasagiline (N-propargyl-1-(R)-aminoindan) is a selective, irreversible monoamine oxidase B (MAO B) inhibitor, which has been developed as an anti-Parkinson drug and was sold as a mesylate salt under brand name AZILECT. AZILECT is indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease (PD) as initial monotherapy and as adjunct therapy to levodopa. The effectiveness of AZILECT was demonstrated in patients with early Parkinson’s disease who were receiving AZILECT as monotherapy and who were not receiving any concomitant dopaminergic therapy. The effectiveness of AZILECT as adjunct therapy was demonstrated in patients with Parkinson’s disease who were treated with levodopa. PD is a progressive neurodegenerative, dopamine deficiency disorder. The main therapeutic strategies for PD treatment relies on dopamine precursors (levodopa), inhibition of dopamine metabolism (monoamine oxidase [MAO] B and catechol-O-methyl transferase inhibitors), and dopamine receptor agonists. In contrast to selegiline, rasagiline is not metabolized to potentially toxic amphetamine metabolites. The precise mechanisms of action of rasagiline is unknown. One mechanism is believed to be related to its MAO-B inhibitory activity, which causes an increase in extracellular levels of dopamine in the striatum.

Anidulafungin (brand names Eraxis (in U.S. and Russia) and Ecalta (in Europe)) is a semi-synthetic echinocandin with antifungal activity and it is active in vitro against many Candida, as well as some Aspergillus. Like other echinocandins, anidulafungin is not active against Cryptococcus neoformans, Trichosporon, Fusarium, or zygomycetes. This drug is indicated for the treatment of candidemia and the following Candida infections: intra-abdominal abscess and peritonitis; and for the treatment of esophageal candidiasis. Anidulafungin inhibits glucan synthase, an enzyme present in fungal, but not mammalian cells. This results in inhibition of the formation of 1,3--D-glucan, an essential component of the fungal cell wall.

Varenicline is a partial nicotinic acetylcholine receptor agonist, designed to partially activate this system while displacing nicotine at its sites of action in the brain. Varenicline is an alpha-4 beta-2 neuronal nicotinic acetylcholine receptor partial agonist. The drug shows high selectiviyty for this receptor subclass, relative to other nicotinic receptors (>500-fold alpha-3 beta-4, >3500-fold alpha-7, >20,000-fold alpha-1 beta gamma delta) or non-nicotinic receptors and transporters (>2000-fold). The drug competitively inhibits the ability of nicotine to bind to and activate the alpha-4 beta-2 receptor. The drug exerts mild agonistic activity at this site, though at a level much lower than nicotine; it is presumed that this activation eases withdrawal symptoms. Varenicline is sold under the trade name Chantix and Champix, it is indicated for use as an aid to smoking cessation treatment.

Deferasirox (marketed as Exjade, Desirox, Deferasirox) is an iron chelator. Its main use is to reduce chronic iron overload in patients who are receiving long term blood transfusions for conditions such as beta-thalassemia and other chronic anemias. It is the first oral medication approved for this purpose in the USA by FDA in November 2005. It is approved in the European Union by the European Medicines Agency (EMA) for children 6 years and older for chronic iron overload from repeated blood transfusions. Deferasirox is highly selective for iron as Fe3+. In approximately 1-year clinical trials of patients with transfusional chronic iron overload associated with beta-thalassaemia, sickle cell disease, myelodysplastic syndrome or other rare chronic anaemias, deferasiroxhad a beneficial effect on liver iron concentrations (LIC) and serum ferritin levels. Deferasirox can cause acute renal failure, fatal in some patients and requiring dialysis in others. It was showed that most fatalities occurred in patients with multiple comorbidities in advanced stages of their hematological disorders.

Arranon is a nucleoside metabolic inhibitor indicated for the treatment of patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. It is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in inhibition of DNA synthesis and cytotoxicity. Administration of nelarabine in combination with adenosine deaminase inhibitors, such 195 as pentostatin, is not recommended. The most common (≥20%) adverse reactions were: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea

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.

Trospium is an antispasmodic, antimuscarinic agent indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency. Receptor assays showed that trospium has negligible affinity for nicotinic receptors as compared to muscarinic receptors at concentrations obtained from therapeutic doses. Trospium antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its parasympatholytic action reduces the tonus of smooth muscle in the bladder. Trospium is marketed under the brand name Sancturain the US, Tropez OD in India,Trosec in Canada, Regurin and Flotros in the United Kingdom and Spasmex in Germany, Russia, Turkey, Argentina, Chile and Israel.