Pathways

Tenofovir is a nucleotide analogue used in the treatment of HIV and chronic hepatitis B. It is taken up into the cell and is subsequently phosphorylated first by adenylate kinases and then by nucleoside diphosphate kinases into tenofovir diphosphate. Tenofovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP) and competes with dATP for binding to the viral DNA polymerase and subsequent incorporation into the growing DNA strand. Once incorporated into the DNA, tenofovir causes chain termination, thus preventing viral replication.

Tenofovir is a nucleotide analog that has shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus. When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell. Tenofovir enters the cell via solute carrier family 22 member 8 and is converted into tenofovir monophosphate by adenylate kinase. Nucleoside diphosphate kinase then converts tenofovir monophosphate into tenofovir diphosphate. Tenofovir diphosphate is an analog of deoxyadenosine triphosphate (dATP). Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Tenofovir alafenamide is a novel tenofovir prodrug nucleoside analog reverse transcriptase inhibitor developed in order to improve renal safety when compared to the counterpart tenofovir disoproxil. It is used for the treatment of chronic hepatitis B virus infection in adults with compensated liver disease. Both of these prodrugs were first created to cover the polar phosphonic acid group on tenofovir by using a novel oxycarbonyloxymethyl linkers to improve the oral bioavailability and intestinal diffusion. In the liver, tenofovir alafenamide is converted into tenofovir alanine by the enzymes Lysosomal protective protein and Liver carboxylesterase 1.Tenofovir alanine is then converted to Tenofovir by the enzyme Histidine triad nucleotide-binding protein 1. It is then transported into the blood via multidrug resistance-associated protein 4 or Solute carrier family 22 then into the infected cell via the same or similar transporters. Tenofovir is then converted to the active metabolite, tenofovir diphosphate, a chain terminator, by constitutively expressed enzymes in the cell. Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and the Hepatitis B polymerase by direct binding in competition with dATP. After integration into DNA, causes viral DNA chain termination. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Tenofovir disoproxil is a prodrug, nucleotide analog reverse transcriptase inhibitor used to treat Hepatitis B infection and used to manage HIV-1 infection. This drug prevents viral DNA chain elongation through inhibition of enzymes necessary for host cell infection viral replication in HIV-1 and Hepatitis B infections. Tenofovir disoproxil fumarate is the fumarate salt of the prodrug tenofovir disoproxil. Tenofovir disoproxil is absorbed and converted to its active form, tenofovir, a nucleoside monophosphate (nucleotide) analog. Tenofovir is then converted to the active metabolite, tenofovir diphosphate, a chain terminator, by constitutively expressed enzymes in the cell. Tenofovir diphosphate inhibits HIV-1 reverse transcriptase and the Hepatitis B polymerase by direct binding in competition with dATP. After integration into DNA, causes viral DNA chain termination. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.

Tenofovir is a nucleotide analogue used in the treatment of HIV and chronic hepatitis B. It is taken up into the cell and is subsequently phosphorylated first by adenylate kinases and then by nucleoside diphosphate kinases into tenofovir diphosphate. Tenofovir diphosphate is an analogue of deoxyadenosine triphosphate (dATP) and competes with dATP for binding to the viral DNA polymerase and subsequent incorporation into the growing DNA strand. Once incorporated into the DNA, tenofovir causes chain termination, thus preventing viral replication.

Tenoxicam (also named mobiflex and tilcotil) is a nonsteroidal anti-inflammatory drug (NSAID). It can be used to reduce inflammation, swelling, stiffness, and pain that are associated with various diseases such as tendinitis, bursitis and etc. Tenoxicam can block prostaglandin synthesis by the action of inhibition of prostaglandin G/H synthase 1 and 2. Prostaglandin G/H synthase 1 and 2 catalyze the arachidonic acid to prostaglandin G2, and also catalyze prostaglandin G2 to prostaglandin H2 in the metabolism pathway. Decreased prostaglandin synthesis in many animal model's cell is caused by presence of tenoxicam.

Tenoxicam is an anti-inflammatory analgesic used to treat mild to moderate pain as well as the signs and symptoms of rheumatoid arthritis and osteoarthritis. It also has antipyretic effects. It targets the prostaglandin G/H synthase-1 (COX-1) and prostaglandin G/H synthase-2 (COX-2) in the cyclooxygenase pathway. The cyclooxygenase pathway begins in the cytosol with phospholipids being converted into arachidonic acid by the action of phospholipase A2. The rest of the pathway occurs on the endoplasmic reticulum membrane, where prostaglandin G/H synthase 1 & 2 converts arachidonic acid into prostaglandin H2. Prostaglandin H2 can either be converted into thromboxane A2 via thromboxane A synthase, prostacyclin/prostaglandin I2 via prostacyclin synthase or prostaglandin E2 via prostaglandin E synthase. COX-2 is an inducible enzyme, and during inflammation, it is responsible for prostaglandin synthesis. It leads to the formation of prostaglandin E2 which is responsible for contributing to the inflammatory response by activating immune cells and for increasing pain sensation by acting on pain fibers. Tenoxicam inhibits the action of COX-1 and COX-2 on the endoplasmic reticulum membrane. This reduces the formation of prostaglandin H2 and therefore, prostaglandin E2 (PGE2). The low concentration of prostaglandin E2 attenuates the effect it has on stimulating immune cells and pain fibers, consequently reducing inflammation and pain. Fever is triggered by inflammatory and infectious diseases. Cytokines are produced in the central nervous system (CNS) during an inflammatory response. These cytokines induce COX-2 production that increases the synthesis of prostaglandin, specifically prostaglandin E2 which adjusts hypothalamic temperature control by increasing heat production. Because tenoxicam decreases PGE2 in the CNS, it has an antipyretic effect. Antipyresis may occur by central action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat loss.