PathWhiz ID | Pathway | Meta Data |
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PW144437View Pathway |
drug action
Vindesine Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 13:38 Last Updated: October 07, 2023 at 13:38 |
PW176358View Pathway |
Vindesine Predicted Metabolism PathwayHomo sapiens
Metabolites of sildenafil are predicted with biotransformer.
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Creator: Omolola Created On: December 07, 2023 at 15:31 Last Updated: December 07, 2023 at 15:31 |
PW146417View Pathway |
drug action
Vinflunine Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 18:09 Last Updated: October 07, 2023 at 18:09 |
PW176164View Pathway |
Vinflunine Predicted Metabolism Pathway newHomo sapiens
Metabolites of Vinflunine are predicted with biotransformer.
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Creator: Omolola Created On: November 29, 2023 at 14:27 Last Updated: November 29, 2023 at 14:27 |
PW000244View Pathway |
drug action
Vinorelbine Action PathwayHomo sapiens
Vinorelbine (also named Navelbine) is a semisynthetic vinca alkaloid. Vinorelbine are used as chemotherapy medication such as an antimitotic anticancer agent. The mechanism of vinorelbine is the inhibition of microtubule dynamics that would cause mitotic arrest and eventual cell death. As a microtubule destabilizing agent, vinorelbine stimulates mitotic spindle destruction and microtubule depolymerization at high concentrations. At lower clinically relevant concentrations, vinorelbine can block mitotic progression. Unlike the taxanes, which bind poorly to soluble tubulin, vinorelbine can bind both soluble and microtubule-associated tubulin. To be able stabilizing the kinetics of microtule, vinorelbine rapidly and reversibly bind to soluble tubulin which can increase the affinity of tublin by the induction of conformational changes of tubulin. Vinorelbine binds to β-tubulin subunits at the positive end of microtubules at a region called the _Vinca_-binding domain. Binding between vinorelbine and solubale tubulin decreases the rate of microtubule dynamics (lengthening and shortening) and increases the duration of attenuated state of microtubules. Therefore, the proper assembly of the mitotic spindle could be prevented; and the tension at the kinetochores of the chromosomes could be reduced. Subsequently, chromosomes can not progress to the spindle equator at the spindle poles. Progression from metaphase to anaphase is blocked and cells enter a state of mitotic arrest. The cells may then undergo one of several fates. The tetraploid cell may undergo unequal cell division producing aneuploid daughter cells. Alternatively, it may exit the cell cycle without undergoing cell division, a process termed mitotic slippage or adaptation. These cells may continue progressing through the cell cycle as tetraploid cells (Adaptation I), may exit G1 phase and undergo apoptosis or senescence (Adaption II), or may escape to G1 and undergo apoptosis during interphase (Adaptation III). Another possibility is cell death during mitotic arrest. Alternatively, mitotic catastrophe may occur and cause cell death. Vinca alkaloids are also thought to increase apoptosis by increasing concentrations of p53 (cellular tumor antigen p53) and p21 (cyclin-dependent kinase inhibitor 1) and by inhibiting Bcl-2 activity. Increasing concentrations of p53 and p21 lead to changes in protein kinase activity. Phosphorylation of Bcl-2 subsequently inhibits the formation Bcl-2-BAX heterodimers. This results in decreased anti-apoptotic activity. One way in which cells have developed resistance against the vinca alkaloids is by drug efflux. Drug efflux is mediated by a number of multidrug resistant transporters as depicted in this pathway.
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Creator: WishartLab Created On: August 22, 2013 at 10:45 Last Updated: August 22, 2013 at 10:45 |
PW124038View Pathway |
drug action
Vinorelbine Action Pathway (New)Homo sapiens
Vinorelbine is a semi-synthetic third generation vinca alkaloid used in chemotherapy treatment for cervical, lung, breast, and esophageal cancers. It is differentiated from natural alkaloids by its eight-catharanine ring. Administered intravenously, vinorelbine acts on tumorous cells in the body to suppress their growth. Its main mechanism of action works by binding microtubules that are formed during the M phase of mitosis. This ceases the polymerization of microtubules, effectively pausing the cell at its G2/M phase. The disarray of microtubules induces two proteins; cellular tumor antigen p53 and cyclin-dependent kinase inhibitor p21. The latter protein works to inhibit cyclin-dependent kinases in the cell, which disrupt the phosphorylation of the apoptosis inhibitor Bcl-2. Bcl-2 suppresses apoptosis by regulating the permeability of the mitochondrial membrane but is unable to do so due to interrupted phosphorylation. The former protein, p53, acts on BAK and BAX to enact conformational changes, creating pores in the mitochondrial membrane that allow the exit of cytochrome c. Cytochrome c further activates caspases in the cell, which cleave essential cellular proteins. In this way, p53 and p21 work alongside each other to promote apoptosis and terminate unhealthy cells. Vinorelbine is especially valuable as a drug because it binds specifically to mitotic microtubules, likely decreasing its neurotoxicity.
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Creator: Alyssah Created On: August 04, 2020 at 16:33 Last Updated: August 04, 2020 at 16:33 |
PW144487View Pathway |
drug action
Vinorelbine Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 13:44 Last Updated: October 07, 2023 at 13:44 |
PW176417View Pathway |
Vinorelbine Predicted Metabolism PathwayHomo sapiens
Metabolites of Vinorelbine are predicted with biotransformer.
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Creator: Omolola Created On: December 07, 2023 at 17:04 Last Updated: December 07, 2023 at 17:04 |
PW128375View Pathway |
drug action
Viomycin Action PathwayHomo sapiens
Viomycin is an antibiotic used to treat Mycobacterium tuberculosis and binds to the ribosome displacing structures leading to inhibition of protein synthesis. It binds to the interface between helix 44 of the small ribosomal subunit and helix 69 of the large ribosomal subunit which stops tRNA from binding to the A site and the addition of amino acids to a polypeptide chain.
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Creator: Selena Created On: August 24, 2023 at 21:10 Last Updated: August 24, 2023 at 21:10 |
PW145827View Pathway |
drug action
Viomycin Drug Metabolism Action PathwayHomo sapiens
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Creator: Ray Kruger Created On: October 07, 2023 at 16:46 Last Updated: October 07, 2023 at 16:46 |