Canagliflozin (INN, trade name Invokana or Sulisent) is a drug of the gliflozin class. It was developed by Mitsubishi Tanabe Pharma and is marketed under license by Janssen, a division of Johnson & Johnson. Canagliflozin is an antidiabetic drug used to improve glycemic control in people with type 2 diabetes. Sodium-glucose co-transporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Canagliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose (RTG), and thereby increases urinary glucose excretion. In extensive clinical trials, canagliflozin produced a consistent dose-dependent reduction in HbA1c of 0.77% to 1.16% when administered as monotherapy, combination with metformin, combination with metformin and a sulfonylurea, combination with metformin and pioglitazone, and in combination with insulin from a baselines of 7.8% to 8.1%, in combination with metformin, or in combination with metformin and a sulfonylurea. When added to metformin, canagliflozin 100 mg was shown to be non-inferior to both sitagliptin 100 mg and glimepiride in reductions on HbA1c at one year, whilst canagliflozin 300 mg successfully demonstrated statistical superiority over both sitagliptin and glimiperide in HbA1c reductions. Secondary efficacy endpoint of superior body weight reduction and blood pressure reduction (versus sitagliptin and glimiperide)) were observed as well. Canagliflozin produces beneficial effects on HDL cholesterol whilst increasing LDL cholesterol to produce no change in total cholesterol.

Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor, indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. SIGNIFOR is an injectable cyclohexapeptide somatostatin analogue. Pasireotide exerts its pharmacological activity via binding to somatostatin receptors (ssts). Pasireotide binds and activates the hsst receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.

Cabozantinib (development code name XL184; marketed under the trade name Cometriq) is an orally bioavailable, small molecule receptor tyrosine kinase (RTK) inhibitor with potential antineoplastic activity. Cabozantinib strongly binds to and inhibits several RTKs, which are often overexpressed in a variety of cancer cell types, including hepatocyte growth factor receptor (MET), RET (rearranged during transfection), vascular endothelial growth factor receptor types 1 (VEGFR-1), 2 (VEGFR-2), and 3 (VEGFR-3), mast/stem cell growth factor (KIT), FMS-like tyrosine kinase 3 (FLT-3), TIE-2 (TEK tyrosine kinase, endothelial), tropomyosin-related kinase B (TRKB) and AXL. This may result in an inhibition of both tumor growth and angiogenesis, and eventually lead to tumor regression. Cabozantinib was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011. It is currently undergoing clinical trials for the treatment of prostate, bladder, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.

Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor discovered by Boehringer Ingelheim and being developed as an oral once-daily tablet for the treatment of Type 2 diabetes. Linagliptin was first approved by FDA in 2011 under the trade name Tradjenta as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Linagliptin binds to DPP-4 (an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) in a reversible manner and thus increases the concentrations of incretin hormones. Linagliptin glucose dependently increases insulin secretion and lowers glucagon secretion, thus resulting in better regulation of glucose homeostasis. Linagliptin binds selectively to DPP-4, and selectively inhibits DPP-4 but not DPP-8 or DPP-9 activity in vitro at concentrations approximating therapeutic exposures.

Cabazitaxel (JEVTANA®) is an antineoplastic agent belonging to the taxane class and is used to treat people with prostate cancer that has progressed despite treatment with docetaxel. It is prepared by semi-synthesis with a precursor extracted from yew needles (10-deacetylbaccatin III). Cabazitaxel (JEVTANA®) is a microtubule inhibitor. It binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. The cell is then unable to progress further into the cell cycle, being stalled at metaphase, thus triggering apoptosis of the cancer cell.

Fingolimod (FTY720) is a sphingosine 1-phosphate receptor modulator indicated and approved for the treatment of relapsing-remitting multiple sclerosis. Fingolimod (trade name Gilenya, Novartis) is metabolized by sphingosine kinase to the active metabolite, fingolimod-phosphate. Fingolimod-phosphate is a sphingosine 1-phosphate receptor modulator, and binds with high affinity to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. The mechanism by which fingolimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve reduction of lymphocyte migration into the central nervous system. Fingolimod was approved as a first-in-class, orally active drug for relapsing multiple sclerosis in 2010, and its applications in other disease conditions are currently under clinical trials.

Pralatrexate (PDX or 10-propargyl-10-deazaaminopterin) is a folate analogue that is internalised by the reduced folate carrier 1 (RFC-1) protein, and polyglutamylated by the enzyme folylpolyglutamyl synthetase (FPGS), resulting in accumulation of the antifolate. Pralatrexate, a methotrexate analogue, is intended as an inhibitor of dihydrofolate reductase (DHFR), an enzyme which catalyses the reduction of dihydrofolic acid to tetrahydrofolic acid. Inhibition of DHFR leads to a depletion of intracellular reduced folate stores, thereby leading to a disruption of DNA synthesis. Preclinical studies in vitro and in models of B-cell lymphomas, T-cell lymphomas and NSCLC indicated that pralatrexate exhibited antitumor activity that was superior to the activity of other antifolates. FOLOTYN (pralatrexate injection) is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma.

Tolvaptan is a selective and competitive arginine vasopressin receptor 2 antagonist. Vasopressin acts on the V2 receptors found in the walls of the vasculature and luminal membranes of renal collecting ducts. By blocking V2 receptors in the renal collecting ducts, aquaporins do not insert themselves into the walls thus preventing water absorption. This action ultimately results in an increase in urine volume, decrease urine osmolality, and increase electrolyte-free water clearance to reduce intravascular volume and an increase serum sodium levels. Tolvaptan is especially useful for heart failure patients as they have higher serum levels of vasopressin. Tolvaptan is used to treat low blood sodium levels (hyponatremia) associated with various conditions like congestive heart failure, cirrhosis, and syndrome of inappropriate antidiuretic hormones (SIADH). FDA approved on May 19, 2009. Tolvaptan is sold under the trade names Samsca and Jinarc.

DEGARELIX (FIRMAGON®) is a synthetic linear decapeptide amide containing seven unnatural amino acids, five of which are D-amino acids. It is a GnRH receptor antagonist. It binds reversibly to the pituitary GnRH receptors, thereby reducing the release of gonadotropins and consequently testosterone. DEGARELIX (FIRMAGON®) is effective in achieving and maintaining testosterone suppression below the castration level of 50 ng/dL and is indicated for the treatment of patients with advanced prostate cancer.

Ambrisentan (alternative Names: BSF 208075; GSK 1325760; GSK1325760A; Letairis) is an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor. The chemical name of ambrisentan is (+)-(2S)-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid. Ambrisentan is indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. As an endothelin receptor antagonist, ambrisentan prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure. Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ETA and ETB, mediate the effects of ET-1 in the vascular smooth muscle and endothelium. The primary actions of ETA are vasoconstriction and cell proliferation, while the predominant actions of ETB are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries. These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (Ki=0.011 nM) ETA receptor antagonist with a high selectivity for the ETA versus ETB receptor (>4000-fold). The clinical impact of high selectivity for ETA is not known.