Repositioning Candidate Details
| Candidate ID: | R1385 |
| Source ID: | DB11626 |
| Source Type: | approved |
| Compound Type: | biotech |
| Compound Name: | Tasonermin |
| Synonyms: | Tasonermin; Tumor necrosis factor, soluble form, nonglycosylated |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Tasonermin is recombinant soluble form tumor necrosis factor α produced via _Escherichia coli_ cell culture. It was approved for use by the European Medicines Agency in April of 1999 for use as an adjunt to surgery for the subsequent removal of the tumor and in palliative care for irresectable soft tissue sarcoma of the limbs as the product Beromun. It is administered with via mild hyperthermic isolated limb perfusion. |
| CAS Number: | 94948-59-1 |
| Molecular Weight: | |
| DrugBank Indication: | For use in adults as an adjunct to surgery for subsequent removal of the tumour so as to prevent or delay amputation, or in palliative care, for irresectable soft tissue sarcoma of the limbs . Used in combination with melphalan via mild hyperthermic isolated limb perfusion. |
| DrugBank Pharmacology: | Tasonermin is thought to contribute to the destruction of tumor tissue via several direct and indirect effects . Tasonermin directly inhibits cell proliferation in a variety of cancer cells. It also modifies endothelial cell morphology and reduces their proliferation in tumor microvasculature. Modification of the expression of cell adhesion proteins, proteins affecting coagulation, interleukins, and hematopoietic growth factors favors a procoagulant state resulting in microvascular thrombosis. These changes also increase infiltration of the tumor tissue by leukocytes. Monocytes, macrophages, and granulocytes are activated allowing better adherence to the endothelium and subjecting the tumor cells to phagocytosis and respiratory bursts as well as producing degranulation of immune cells to further enhance inflammatory activity. Active antigen presenting cells are able to activate and induce proliferation of T- and B-lymphocyte cells to allow the adaptive immune system to contribute to tumor cell damage. These changes lead to hemorraghic necrosis of the tumor. |
| DrugBank MoA: | Since tasonermin is recombinant TNF-α, it functions exactly as endogenous TNF-α does. The direct cytotoxic effect of TNF-α is mediated by TNF-α receptor 1 . The bound receptor activates the well-reviewed death receptor pathway involving the activation of initiator caspases 8 and 9 then ultimately ending in the activation of effector caspase 3 which begins the process of apoptosis. The effect on tumor vasculature is mediated by the inflammatory signalling pathway of TNF-α, the NFκB pathway . This pathway is also activated by TNFR1 when bound to TNFα. The NFκB transcription factor increases expression of proteins in vascular endothelial cells. These proteins include cell adhesion molecules, inflammatory mediators like prostaglandins and interleukins, and growth factors . TNF-&alpha also increases the expression of inducible nitric oxide synthase via this pathway which contributes to the generation of reactive nitrogen species . These species are able to damage cells in the tumor and microvasculature. The cytokines produced from NFκB activation and TNF-&aplha; itself serve to activate the cells of the immune system which further damage tumor cells with respiratory bursts, phagocytosis and subsequent breakdown of the cell, and release of cytotoxic enzymes. The antigen presenting cells which phagocytose the tumor cells are able to activate lymphocytes and allow the adaptive immune system to further damage the tumor tissue . |
| Targets: | Tumor necrosis factor receptor superfamily member 1A agonist; Tumor necrosis factor receptor superfamily member 1B agonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class |
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