Infigratinib (BGJ398), a potent, orally bioavailable, small-molecule pan-FGFR kinase inhibitor. FGFR genetic alterations are the most significant predictors for BGJ398 sensitivity. It is currently in phase 2 trials for Cholangiocarcinoma, Glioblastoma and Solid tumors. Detected adverse events were hyperphosphatemia, fatigue, constipation, cough and nausea. Other adverse events were generally mild and included stomatitis, hair loss, decreased appetite, and fatigue.

Infigratinib (BGJ398), a potent, orally bioavailable, small-molecule pan-FGFR kinase inhibitor. FGFR genetic alterations are the most significant predictors for BGJ398 sensitivity. It is currently in phase 2 trials for Cholangiocarcinoma, Glioblastoma and Solid tumors. Detected adverse events were hyperphosphatemia, fatigue, constipation, cough and nausea. Other adverse events were generally mild and included stomatitis, hair loss, decreased appetite, and fatigue.

Oliceridine (TRV-130) is a potent μ-opioid receptor agonist. In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β-arrestin recruitment and receptor internalization. In rodents, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses. Oliceridine is being developed by Trevena for the first-line treatment of moderate-to-severe acute postoperative pain. Phase III development is underway for the treatment of postoperative pain in the US. Phase II development is underway for the treatment of acute pain in the US.

Oliceridine (TRV-130) is a potent μ-opioid receptor agonist. In cell-based assays, TRV130 elicits robust G protein signaling, with potency and efficacy similar to morphine, but with far less β-arrestin recruitment and receptor internalization. In rodents, TRV130 is potently analgesic while causing less gastrointestinal dysfunction and respiratory suppression than morphine at equianalgesic doses. Oliceridine is being developed by Trevena for the first-line treatment of moderate-to-severe acute postoperative pain. Phase III development is underway for the treatment of postoperative pain in the US. Phase II development is underway for the treatment of acute pain in the US.

Panobinostat is an oral deacetylace (DAC) inhibitor approved on February 23, 2015 by the FDA for the treatment of multiple myeloma. The approval was accelerated based on progression-free survival, therefore confirmatory trials by the sponsor to demonstrate clinical efficacy in multiple myeloma treatment are in progress of being conducted. Panobinostat is marketed by Novartis under the brand name Farydak. Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.

Daclatasvir (BMS-790052) is a direct-acting antiviral agent against Hepatitis C Virus (HCV) used for the treatment of chronic HCV genotype 3 infection. Daclatasvir prevents RNA replication and virion assembly by binding to NS5A, a nonstructural phosphoprotein encoded by HCV. Binding to the N-terminus of the D1 domain of NS5A prevents its interaction with host cell proteins and membranes required for virion replication complex assembly.

Yohimbine is a plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. The exact mechanism for its use in impotence has not been fully elucidated. Yohimbine exerts antagonist actions at halpha(2A)-AR, h5-HT(1B), h5-HT(1D), and hD(2) sites, partial agonist actions at h5-HT(1A) sites. Yohimbine-mediated norepinephrine release at the level of the corporeal tissues may also be involved. In addition, beneficial effects may involve other neurotransmitters such as dopamine and serotonin and cholinergic receptors. Yohimbine has a mild anti-diuretic action, probably via stimulation of hypothalmic center and release of posterior pituitary hormone. Reportedly yohimbine exerts no significant influence on cardiac stimulation and other effects mediated by (beta)-adrenergic receptors. Its effect on blood pressure, if any, would be to lower it; however, no adequate studies are at hand to quantitate this effect in terms of Yohimbine dosage. Side effect of Yohimbine include anxiety, tremor, palpitations, diarrhea, and supine hypertension.

Vorapaxar is a tricyclic himbacine-derived oral thrombin receptor antagonist that acts by reversible inhibition of the protease-activated receptor-1 (PAR-1). PAR-1 is expressed on platelets and its inhibition prevents platelets from aggregation. Vorapaxar is approved by FDA and is indicated for the reduction of recurring thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. Vorapaxar at the same time may cause bleeding complications including intracranial haemorrhage (ICH), when compared to standard therapy alone. That is why Vorapaxar is contraindicated in patients with prior stroke, transient ischemic attack and ICH.

Lorcaserin, currently marketed under the trade name Belviq and previously Lorqess during development, is a weight-loss drug developed by Arena Pharmaceuticals. Lorcaserin is a selective 5-HT2C receptor agonist, and in vitro testing of the drug showed reasonable selectivity for 5-HT2C over other related targets. 5-HT2C receptors are located almost exclusively in the brain, and can be found in the choroid plexus, cortex, hippocampus, cerebellum, amygdala, thalamus, and hypothalamus. The activation of 5-HT2C receptors in the hypothalamus is supposed to activate proopiomelanocortin (POMC) production and consequently promote weight loss through satiety. This hypothesis is supported by clinical trials and other studies. While it is generally thought that 5-HT2C receptors help to regulate appetite as well as mood, and endocrine secretion, the exact mechanism of appetite regulation is not yet known. Lorcaserin has shown 100x selectivity for 5-HT2C versus the closely related 5-HT2B receptor, and 17x selectivity over the 5-HT2A receptor

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.