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.

Cangrelor is a P2Y12 inhibitor that has been approved as an antiplatelet drug. It is marketed in the US under the brand name Kengreal and in Europe as Kengrexal. Cangrelor is an intravenous, direct-acting reversible P2Y12 inhibitor for patients undergoing percutaneous coronary intervention.

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.

Ceritinib is a selective inhibitor of ALK1, a target found in metastatic non-small cell lung cancer (NSCLC). Ceritinib is approved by FDA and is indicated for the treatment of anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer. Ceritinib also targets insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1.

Miltefosine is an anti-leishmanial agent. It is an alkyl phospholipids compound, was originally intended for breast cancer and other solid tumors. However, it could not be developed as an oral agent because of dose-limiting gastro-intestinal toxicity, and only a topical formulation is approved for skin metastasis. But Miltefosine showed excellent antileishmanial activity both in vitro and in experimental models. Miltefosine is effective in vitro against both promastigotes and amastigotes of various species of Leishmania and also other kinetoplastidae (Trypanosoma cruzi,T. brucei) and other protozoan parasites (Entamoeba histolytica, Acanthamoeba). Mechanism of action is unknown. It is likely to involve interaction with lipids (phospholipids and sterols), including membrane lipids, inhibition of cytochrome c oxidase (mitochondrial function), and apoptosis-like cell death. Miltefosine is approved for the treatment of Visceral leishmaniasis (due to Leishmania donovani), Cutaneous leishmaniasis (due to Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis) and Mucosal leishmaniasis (due to Leishmania braziliensis).

Tedizolid phosphate is an oxazolidinone prodrug which in the body is dephosphorylated to the active compound tedizolid. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. Tedizolid is bacteriostatic against Gram Positive bacteria such as enterococci, staphylococci, and streptococci. No drug-drug interactions were identified with tedizolid.

Efinaconazole is triazole used as a 10% topical solution for the treatment of onychomycosis, a fungal infection of the nails. It was approved for use in Canada and the USA in 2014 and is marketed by Valeant Pharmaceuticals North America LLC under the name Jublia. Like other antifungal triazoles, efinaconazole inhibits the fungal cytochrome P450 enzyme lanosterol 14α demethylase (CYP51), thereby disrupting ergosterol synthesis and, consequently, membrane integrity and growth in fungi. CYP51 is evolutionarily conserved and, in mammals, mediates conversion of lanosterol to meiosis-activating sterols (MAS); MAS are intermediates in the biosynthesis of cholesterol and may have a signaling role in initiating meiosis and oocyte maturation. Azoles have higher affinity for fungal CYP51 compared to the mammalian enzyme and such selectivity contributes to the safety of this therapeutic class. Azoles have been reported to produce reproductive and developmental toxicity in both humans and laboratory animals. The mechanism is unknown but inhibition of mammalian CYP51 as well as other CYPs, e.g. CYP17, CYP19 and CYP26, have been postulated to play a role.

Dehydroepiandrosterone (INTRAROSA™, prasterone) is a major C19 steroid produced from cholesterol by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (INTRAROSA, prasterone) is structurally similar to, and is a precursor of, androstenedione, testosterone, estradiol, estrone and estrogen. It indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. The mechanism of action of dehydroepiandrosterone (INTRAROSA, prasterone) in postmenopausal women with vulvar and vaginal atrophy is not fully established.

Fosnetupitant is a prodrug form of netupitant. Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK-1) receptors. Upon intravenous administration, fosnetupitant is converted by phosphatases to its active form. It competitively binds to and blocks the activity of NK-1 receptors in the central nervous system, by inhibiting binding of substance P (SP) to NK-1 receptors. This prevents delayed emesis, which is associated with SP secretion. AKYNZEO® is a combination of palonosetron, a serotonin-3 receptor antagonist, and netupitant (capsules for oral use) or fosnetupitant (injections for intravenous use). AKYNZEO® for injection is indicated in combination with dexamethasone in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy.

Olodaterol is a beta2-adrenoceptor agonist discovered by Boehringer Ingelheim and approved for the treatment of Chronic Obstructive Pulmonary Disease. The compound exerts its pharmacological effects by binding and activation of beta2-adrenoceptors after inhalation. Activation of these receptors in the airways results in a stimulation of intracellular adenyl cyclase, an enzyme that mediates the synthesis of cyclic-3’, 5’ adenosine monophosphate (cAMP). Elevated levels of cAMP induce bronchodilation by relaxation of airway smooth muscle cells. Olodaterol effect lasts for 24 hours.