Dabrafenib is a selective, orally bioavailable inhibitor of Mutant BRAF protein kinase with potential antineoplastic activity. Dabrafenib inhibits BRAF kinases with in vitro IC50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC50 values of 3.2 and 5.0 nM. BRAF belongs to the the raf/mil family of serine/threonine protein kinases and plays a role in regulating the MAP kinase/ERKs signaling pathway, which may be constitutively activated due to BRAF gene mutations. Mutations in BRAF are associated with increased growth and proliferation of cancer cells. By inhibiting BRAF kinase dabrafenib negatively regulates the proliferation of tumor cells which contain a mutated BRAF gene. Dabrafenib (in combination with trametinib or alone) is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E mutation

Trametinib is a reversible and specific inhibitor of mitogen-activated protein kinase kinases MEK1 and MEK2 which are involved in a RAS/RAF/MEK/ERK signaling pathway and control cell growth, survival, and differentiation. By inhibiting MEK1 and MEK2 trametinib blocks dual phosphorylation of ERK1/2 and stops cell cycling. In addition, trametinib blocks BRAF pathway in the cells with BRAF V600E mutations. Trametinib (as a single agent and in combination with dabrafenib) is approved for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations.

Vilanterol (INN, USAN) is an ultra-long-acting β2 adrenoreceptor agonist (ultra-LABA), which was approved in May 2013 in combination with fluticasone furoate for sale as Breo Ellipta by GlaxoSmithKline for the treatment of chronic obstructive pulmonary disease (COPD). Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3’,5’-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs. Vilanterol is available in following combinations: a) with inhaled corticosteroid fluticasone furoate — fluticasone furoate/vilanterol (trade names Breo Ellipta , Relvar Ellipta; b) with muscarinic antagonist umeclidinium bromide — umeclidinium bromide/vilanterol (trade name Anoro Ellipta).

Luliconazole (trade names Luzu, Lulicon) is an imidazole antifungal drug. As a 1% topical cream, It is indicated for the treatment of athlete's foot, jock itch, and ringworm caused by dermatophytes such as Trichophyton rubrum, Microsporum gypseum and Epidermophyton floccosum. Luliconazole is an antifungal that belongs to the azole class. Although the exact mechanism of action against dermatophytes is unknown, luliconazole appears to inhibit ergosterol synthesis by inhibiting the enzyme lanosterol demethylase. Inhibition of this enzyme’s activity by azoles results in decreased amounts of ergosterol, a constituent of fungal cell membranes, and a corresponding accumulation of lanosterol. Pharmacokinetic and safety results from phase 1 studies in patients with onychomycosis have demonstrated high concentrations of luliconazole within the nail plates of the great toe and have shown that this agent is well tolerated when administered as a 10% solution.

Afatinib is a anilino-quinazoline derivative and irreversible antagonist of the receptor tyrosine kinase epidermal growth factor receptor family, with antineoplastic activity. Afatinib selectively and covalently binds to and inhibits the epidermal growth factor receptors 1 (ErbB1; EGFR), 2 (ErbB2; HER2), and 4 (ErbB4; HER4), and certain EGFR mutants, including those caused by EGFR exon 19 deletion mutations or exon 21 (L858R) mutations. This may result in the inhibition of tumor growth and angiogenesis in tumor cells overexpressing these kinases. Additionally, afatinib inhibits the EGFR T790M gatekeeper mutation which is resistant to treatment with first-generation EGFR inhibitors. EGFR, HER2 and HER4 are RTKs that belong to the EGFR superfamily; they play major roles in both tumor cell proliferation and tumor vascularization and are overexpressed in many cancer cell types. Afatinib is a substrate and an inhibitor of P-gp and of the transporter BCRP. Co-administration of P-gp inhibitors can increase afatinib exposure while co-administration of chronic P­gp inducers can decrease afatinib exposure.

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.

Umeclidinium (used as a bromide salt) is a long-acting, antimuscarinic antagonist, often referred to as an anticholinergic, developed for the treatment of chronic obstructive pulmonary disease (COPD) (alone and in combination with Vilanterol - long-acting beta2-adrenergic agonist). Umeclidinium has similar affinity to the subtypes of muscarinic receptors M1 to M5 with Ki values of 0.16 nM, 0.15 nM, 0.06 nM, 0.05 nM and 0.13 nM for M1, M2, M3, M4 and M5, respectively. Umeclidinium is selective against mAChR over other unrelated receptors or channels such as κ and σ opiod receptors, Na+ channel and dopamine transporter. In the airways, it exhibits pharmacological effects through the inhibition of M3 receptor at the smooth muscle leading to bronchodilation. There is potential for an additive interaction with concomitantly used anticholinergic medicines.

Triheptanoin (also known as C7 oil) is an investigational medical food or supplement. Triheptanoin is thought to have an anaplerotic role, meaning that it can replenish substances involved in the tricarbolic acid cycle, a pathway used by cells to produce energy, providing an alternative source of energy to the brain. It supplies the body with heptanoate which can either be oxidized to propionyl-CoA directly or is metabolized by the liver to the“C5 ketones”, β-ketopentanoate and/or β-hydroxypentanoate, which are released into the blood. After one month of triheptanoin use, the level of energy production in the brain during visual stimulation had become normal in Huntington’s patients. Triheptanoin was anticonvulsant in two chronic mouse models and increased levels of anaplerotic precursor metabolites in epileptic mouse brains. Despite the unknown mechanism of triheptanoin’s anticonvulsant action, the fact that triheptanoin has been used safely in several animals and for various metabolic diseases in children and adults should expedite the ethical and regulatory approval processes for a clinical trial in medically refractory patients with epilepsy. Triheptanoin is phase II clinical trial for the treatment of glycogen storage disease type V, Huntington's disease, Rett syndrome and amyotrophic lateral sclerosis.

Avanafil is a PDE5 inhibitor approved for erectile dysfunction by FDA and by EMA. Avanafil is known by the trademark names Stendra and Spedra and was developed by Vivus Inc. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Avanafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has noeffect in the absence of sexual stimulation. The advantage of avanafil is that it has very fast onset of action compared with other PDE5 inhibitors. It is absorbed quickly, reaching a maximum concentration in about 30–45 minutes. About two-thirds of the participants were able to engage in sexual activity within 15 minutes.

Omacetaxine mepesuccinate (trade name Synribo) formerly named as homoharringtonine or HHT, is a pharmaceutical drug substance that is indicated for treatment of chronic myeloid leukemia (CML). It is a natural ester of the alkaloid cephalotaxine from Cephalotaxus harringtonia, now manufactured by hemi-synthesis. It was approved by the US FDA in October 2012 for the treatment of adult patients with CML with resistance and/or intolerance to two or more tyrosine kinase inhibitors (TKIs). The mechanism of action of omacetaxine mepesuccinate has not been fully elucidated but includes inhibition of protein synthesis and is independent of direct Bcr-Abl binding. Omacetaxine mepesuccinate binds to the A-site cleft in the peptidyl-transferase center of the large ribosomal subunit from a strain of archaeabacteria. In vitro, omacetaxine mepesuccinate reduced protein levels of the Bcr Abl oncoprotein and Mcl-1, an anti-apoptotic Bcl-2 family member. Omacetaxine mepesuccinate showed activity in mouse models of wild-type and T315I mutated Bcr-Abl CML.