Browsing Pathways

Voxilaprevir is a nonstructural protein 3 and 4a protease inhibitor used to treat Hepatitis C infections. Hepatitis C virus lipoviroparticles enter target hepatocytes via receptor-mediated endocytosis. The lipoviroparticles attach to LDL-R and SR-B1, and then the virus binds to CD81 and subsequently claudin-1 and occludin, which mediate the late steps of viral entry. The virus is internalized by clathrin-dependent endocytosis. RNA is released from the mature Hepatitis C virion and translated at the rough endoplasmic reticulum into a single Genome polyprotein. Voxilaprevir accumulates in the liver after uptake into hepatocytes via solute carrier organic anion transporter family member 1B1. Voxilaprevir inhibits NS3/4A protease, which is an enzyme that cleaves the heptatitis C virus polyprotein downstream of the NS3 proteolytic site, which generates nonstructural proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins are required in viral RNA replication, therefore because of the inhibition of their formation, RNA replication cannot occur. Because RNA replication does not occur, the mature virion is unable to form.

Vortioxetine is classified as a serotonin modulator and simulator (SMS) as it has a multimodal mechanism of action towards the serotonin neurotransmitter system whereby it simultaneously modulates one or more serotonin receptors and inhibits the reuptake of serotonin. More specifically, vortioxetine acts via the following biological mechanisms: as a serotonin reuptake inhibitor (SRI) through inhibition of the serotonin transporter, while also acting as a partial agonist of the 5-HT1B receptor, an agonist of 5-HT1A, and antagonist of the 5-HT3, 5-HT1D, and 5-HT7 receptors

Voriconazole is an triazole antifungal medication used to treat serious, invasive fungal infections. It has increased affinity to 14-alpha sterol demethylase which means it is useful against Fluconazole-resistant organisms. Voriconazole is taken either orally or injected intravenously. The bioavailability of voriconazole is 96%. When taken orally it is transported from the intestine into the intestinal epithelial cell possibly via solute carrier family 15 member 1, one of 3 drug transporters into epithelial cells. It is then transported into blood vessels via ATP-binding cassette sub-family C member 3. It is then transported through the blood to the liver where it is transported in by a liver drug transporter like solute carrier family 22 member 1. On the endoplasmic reticulum membrane Voriconazole is metabolized into Voriconazole N-Oxide by Cytochrome P450 2C9, Cytochrome P450 2C19, Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7, which makes up 72% of metabolites found. Voriconazole N-Oxide is metabolized into a voriconazole related compound (UK-51,060) by an unknown enzyme. That is predicted by biotransformer to be metabolized by Carbonyl reductase [NADPH] 1 into a similar voriconazole related compound (UK-215,364). That is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into Voriconazole O-glucuronide derivative (1). Voriconazole also metabolizes into 4-Hydroxyvoriconazole via the enzymes Cytochrome P450 3A4, Cytochrome P450 3A5, or Cytochrome P450 3A7. 4-Hydroxyvoriconazole is predicted by biotransformer to be metabolized by UDP-glucuronosyltransferase 1-3 into 4-Hydroxyvoriconazole 4-O-glucuronide. Voriconazole and all the metabolites are transported out of the liver and into blood vessels by a transport protein such as multidrug resistance-associated protein 4. They all then travel to the kidney where they are excreted in the urine. Less than 2% of the dose is excreted as unchanged voriconazole. 72% is excreted as the metabolite voriconazole N-oxide.