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.

Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.

Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015. Palbociclib is marketed under the trade name Ibrance. IBRANCE is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.

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.

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.

Alectinib is a second generation oral drug that selectively inhibits the activity of anaplastic lymphoma kinase (ALK) tyrosine kinase. It was developed by Chugai Pharmaceutical Co. Japan, which is part of the Hoffmann-La Roche group. Alectinib is specifically used in the treatment of non-small cell lung cancer (NSCLC) expressing the ALK-EML4 (echinoderm microtubule-associated protein-like 4) fusion protein that causes proliferation of NSCLC cells. Inhibition of ALK prevents phosphorylation and subsequent downstream activation of STAT3 and AKT resulting in reduced tumour cell viability. Approved under accelerated approval in 2015, alectinib is indicated for use in patients who have progressed on or were not tolerant of crizotinib, which is associated with the development of resistance. Alectinib is marketed as Alecensa.

Osimertinib is an oral, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) drug developed by AstraZeneca Pharmaceuticals. Its use is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in cases where tumour EGFR expression is positive for the T790M mutation as detected by FDA-approved testing and which has progressed following therapy with a first-generation EGFR tyrosine kinase inhibitor. Approximately 10% of patients with NSCLC have a rapid and clinically effective response to EGFR-TKIs due to the presence of specific activating EGFR mutations within the tumour cells. More specifically, deletions around the LREA motif in exon 19 and exon 21 L858R point mutations are correlated with response to therapy. Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that binds to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) that predominate in non-small cell lung cancer (NSCLC) tumours following treatment with first-line EGFR-TKIs. As a third-generation tyrosine kinase inhibitor, osimertinib is specific for the gate-keeper T790M mutation which increases ATP binding activity to EGFR and results in poor prognosis for late-stage disease. Furthermore, osimertinib has been shown to spare wild-type EGFR during therapy, thereby reducing non-specific binding and limiting toxicity. Osimertinib is marketed under the brand name Tagrisso.

Eluxadoline, an orally active mixed μ opioid receptor (μOR) agonist δ opioid receptor (δOR) antagonist. Eluxadoline normalizes gastrointestinal (GI) transit and defecation under conditions of novel environment stress or post-inflammatory altered GI function. Allergan (previously Actavis) is developing eluxadoline for the treatment of diarrhoea-predominant irritable bowel syndrome. The agent was originated by Janssen Pharmaceutica. Eluxadoline has been launched in the US under trade name VIBERZI (eluxadoline) tablets, while is at the preregistration stage in the EU.