Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

Safinamide (FCE 26743, NW 1015, PNU 151774, PNU 151774E, trade name Xadago) combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide is under development with Newron, Zambon and Meiji Seika Pharma for the treatment of Parkinson's disease. Safinamide has been launched in the EU, Iceland and Liechtenstein. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa.

Neratinib (HKI-272) is a pan-HER inhibitor, this irreversible tyrosine kinase inhibitor binds and inhibits the tyrosine kinase activity of epidermal growth factor receptors, EGFR (or HER1), HER2 and HER4, which leads to reduced phosphorylation and activation of downstream signaling pathways. Neratinib is a modified form of the discontinued compound pelitinib, and was originally being develoAdditionally, phase II development of oral neratinib as a neoadjuvant therapy for breast cancer, as a second-line therapy for non-small cell lung cancer, and for other solid tumours is also in progress in numerous countries worldwide. ped by Wyeth (later Pfizer). Oral neratinib is awaiting approval as an extended adjuvant therapy for breast cancer in the EU and in the US. Blocking HER2 function by a small molecule kinase inhibitor, such as neratinib, represents an attractive alternate strategy for the growth inhibition of HER2-positive tumours.

Safinamide (FCE 26743, NW 1015, PNU 151774, PNU 151774E, trade name Xadago) combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide is under development with Newron, Zambon and Meiji Seika Pharma for the treatment of Parkinson's disease. Safinamide has been launched in the EU, Iceland and Liechtenstein. Safinamide was well tolerated and safe in the clinical development program that demonstrated the amelioration of motor symptoms and OFF phenomena by safinamide when combined with dopamine agonists or levodopa.

Delafloxacin (CAS registry number 189279-58-1) was described as WQ-3034 by Wakunaga Pharmaceutical Co., Ltd., Osaka & Hiroshima, Japan. It was first licensed in 1999 to Abbott Park, IL, and further developed as ABT-492. Delafloxacin (Baxdela), a fluoroquinolone antibiotic, is currently being developed by Melinta Therapeutics. It is a novel investigational fluoroquinolone in development for the treatment of uncomplicated gonorrhea, and acute bacterial skin and skin structure infections. Delafloxacin shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. Delafloxacin is a dual-targeting fluoroquinolone, capable of forming cleavable complexes with DNA and topoisomerase IV or DNA gyrase and of inhibiting the activity of these enzymes in both Gram-positive and Gram-negative bacteria. On Oct 24, 2016, Melinta Therapeutics Submitted Baxdela New Drug Application for hospital-treated skin infections.

Isavuconazole is an active form of isavuconazonium, a prodrug which is marketed under the name Cresemba. Isavuconazole inhibits lanosterol 14-alpha demethylase (or CYP51A1) and leads to the accumulation of ergosterol toxic precursors in the fungal cytoplasm. Isavuconazole is indicated for the treatment of invasive aspergillosis and invasive mucormycosis.

Uridine triacetate (formally PN401) is an acetylated prodrug of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. Uridine triacetate under VISTOGARD trade name is a uridine replacement agent approved for the emergency treatment of fluorouracil or capecitabine overdose (regardless of the presence of symptoms) or early-onset severe or life-threatening cardiac or central nervous system (CNS) toxicity and/or early-onset unusually severe adverse reactions (eg, gastrointestinal [GI] toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration in adult and pediatric patients. Uridine competitively inhibits cell damage and cell death caused by fluorouracil. Fluorouracil is a cytotoxic antimetabolite that interferes with nucleic acid metabolism in normal and cancer cells. Cells anabolize fluorouracil to the cytotoxic intermediates 5-fluoro-2’-deoxyuridine-5’- monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). FdUMP inhibits thymidylate synthase, blocking thymidine synthesis. Thymidine is required for DNA replication and repair. Uridine is not found in DNA. The second source of fluorouracil cytotoxicity is the incorporation of its metabolite, FUTP, into RNA. This incorporation of FUTP into RNA is proportional to systemic fluorouracil exposure. Excess circulating uridine derived from VISTOGARD is converted into uridine triphosphate (UTP), which competes with FUTP for incorporation into RNA. Uridine triacetate is also approved for the treatment of hereditary orotic aciduria under XURIDEN trade name. Uridine triacetate provides uridine in the systemic circulation of patients with hereditary orotic aciduria who cannot synthesize adequate quantities of uridine due to a genetic defect in uridine nucleotide synthesis.

Sacubitril is a prodrug neprilysin inhibitor used in combination with valsartan (sold under the brand name Entresto among others) to reduce the risk of cardiovascular events in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction. It was approved under the FDA's priority review process for use in heart failure on July 7, 2015. Sacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natiuretic peptides such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and also vasoconstrictors such as angiotensin I and II, endothelin-1 and peptide amyloid beta-protein. Inhibition of neprilysin therefore leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II.

Isavuconazole is an active form of isavuconazonium, a prodrug which is marketed under the name Cresemba. Isavuconazole inhibits lanosterol 14-alpha demethylase (or CYP51A1) and leads to the accumulation of ergosterol toxic precursors in the fungal cytoplasm. Isavuconazole is indicated for the treatment of invasive aspergillosis and invasive mucormycosis.

Isavuconazole is an active form of isavuconazonium, a prodrug which is marketed under the name Cresemba. Isavuconazole inhibits lanosterol 14-alpha demethylase (or CYP51A1) and leads to the accumulation of ergosterol toxic precursors in the fungal cytoplasm. Isavuconazole is indicated for the treatment of invasive aspergillosis and invasive mucormycosis.