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Tissue Necrosis Factor and Tyrosine Kinase Inhibitor

Let’s move on to another therapeutic class which is tissue necrosis factor or the TNF. Now TNF also belongs to a group of cytokine. And they are produced by monocyte and macrophage. And once they are produced, you can tell, they increase the differentiation of other cells. They control the T cell proliferation. They control the formation of antibody. They control the apoptosis. And they also increased self infiltration and the angiogenesis. And again, you would not be surprised, if someday, in the future, that one or combination of these pathways lead to the discovery of a new biologics. TNF functions or tissue necrosis factor functions First, the modulation of immunological response. And the modulation of the inflammatory response. Modulation of cell differentiation and proliferation.
And lastly, the autoimmune application. The TNF types. TNF alpha is a cytotoxic or cytotoxin that causes tumor cell death or the apoptosis of the tumor cell. And that’s why you divide the name tissue necrosis factor, because it causes the tissue to become dead. TNF-beta. It’s a lymphotoxin. And the TNF blockers or antagonist, those are the ones that blocked the TNF receptors. Let’s look at the product. The TNF blockers are to turn out to be most economically beneficial. For example, the Humira, in 2010, seven billion dollars a year. So it’s a single-use pre-filled syringe, given SC every two weeks, self-injection. Embryo, 8 billion dollars a year in 2010. That was a single-use pre-filled syringe.
Remicade or infliximab, again another 8 billion dollars a year. This one does require infusion in the doctor’s office, okay. But prefilled syringes could be coming on the market as well. So this is Remicade. This is embryo, and as you can tell, embryo has prefilled syringes. Another type of therapeutic category, tyrosine kinase inhibitor. So what is Tyrosine Kinase? It is a protein kinase that catalyzes the phosphorylation of the protein. And this reaction is an on and off reaction. However, for some reason, if it’s kept on, and that leads to overgrowth of cells. And overgrowth of cells manifests into cancer. So if we can block this Tyrosine Kinase, we will be able to block the process to let the cells overgrow.
And that is to stop the formation of cancer or cancer cells. And these are the tyrosine kinase inhibitors, Gleevec. It is also a PDFG-R. It’s a platelet-derived growth factor receptor. And it’s indicated for chronic myelogenous leukemia. Nintedanib or trade name Ofev. It’s indicated for idiopathic pulmonary fibrosis(IPF). Yet another product Ceritinib. It’s indicated for non-small cell lung cancer. And lastly the one is Eisai, Lenvatinib. It’s also a EGFR inhibitor and it’s indicated for differentiated thyroid cancer. And I just want to quickly show you the packages. I understand that they are going to change, but as always when you look at the product and the package, pay attention to dose or dosage strength.

Tumor necrosis factor (TNF) is a multifunctional cytokine that plays important roles in diverse cellular functions such as cell survival, proliferation, differentiation, and death. As a pro-inflammatory cytokine, TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. A tyrosine kinase inhibitor (TKI) is a pharmaceutical drug that inhibits tyrosine kinases. Being small molecule in chemical nature, TKIs are not biologics by traditional definition.

Mechanisms of TNF and TNF blockade, and for tyrosine kinase inhibition are both shown in the sketch. TNF functions include: modulation of immunological response, inflammatory response, and cell differentiation and proliferation Depending on the dominant functionality, TNFs or TNF inhibitors convey autoimmune, anti-inflammatory or anti-cancer application. They are two types of TNFs, TNF alpha and TNF beta; both are cytotoxins that are chemotherapeutically anti-cancerous. TNF blockers enjoy much greater therapeutic success than TNFs, three of the most widely marketed anti-inflammatory for rheumatoid arthritis are adalimumab, etanercept and infliximab. All tyrosine kinase inhibitors are named with a suffix –nib, for example, Imatinib, nintendanib, ceritinib and lenvatinib, whose indication is mostly anti-cancerous

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