The product is made from a human protein, Interleukin 13 (IL13), linked to a bacterial toxin, Pseudomonas exotoxin (PE). The IL13 portion binds to receptors on the tumor.
>99% by SDS-Page and HPLC analysis
<0.001 EU per 1 μg of the peptide by the LAL method
Investigated for use/treatment in brain cancer.
Examples of Clinical Use:
Mechanism of action:
A recombinant chimeric protein with potent antitumor activity. Cintredekin besudotox is composed of interleukin-13 (IL13), a pleiotropic immunoregulatory cytokine, linked to a mutated form of pseudomonas exotoxin A; this agent targets and kills tumor cells that express the IL13 receptor (IL13R). The IL13 moiety attaches to the IL13R on the tumor cell membrane, facilitating the entry of the exotoxin. The exotoxin moiety induces caspase-mediated apoptosis of tumor cells via a mechanism involving mitochondrial damage; it also catalyzes the transfer of ADP ribose from nicotinamide adenine dinucleotide (NAD) to elongation factor-2 in eukaryotic cells, thereby inactivating elongation factor 2 and inhibiting protein synthesis.
The human IL13 protein, also known as interleukin-13, is a cytokine that plays a crucial role in the immune system. It was discovered in 1993 as a product of activated CD4+ T cells. IL13 is primarily produced by Th2 cells, mast cells, and basophils. It is encoded by the IL13 gene located on chromosome 5q31.1. The protein structure of IL13 consists of four alpha-helices, and it forms a four-helix bundle.
Function of Human IL13 Protein
The primary function of human IL13 protein is to regulate inflammatory responses and immune system activity. It is involved in various physiological processes, including the regulation of B-cell differentiation and immunoglobulin production. IL13 also induces the production of mucus and airway hyper-responsiveness in conditions such as asthma. Additionally, IL13 contributes to tissue remodeling, fibrosis, and allergic responses.
Signaling Pathways Related to Human IL13 Protein
The signaling pathways associated with human IL13 protein are crucial for mediating its effects. IL13 binds to its receptor, IL13Rα1, which leads to the recruitment of IL4Rα. This complex activates several downstream pathways, including the JAK-STAT signaling pathway. Through this pathway, IL13 regulates gene expression, modulating immune responses and inflammation.
Another important pathway activated by IL13 is the MAPK signaling pathway. This pathway plays a role in cell survival, proliferation, and differentiation. IL13 also activates the PI3K-AKT signaling pathway, promoting cell growth, survival, and migration. These signaling pathways collectively contribute to the immune response regulated by IL13.
IL13 Protein-Related Diseases and Roles in Diseases
The dysregulation of IL13 signaling has been implicated in various diseases. One prominent example is asthma, where IL13 contributes to airway inflammation, mucus production, and bronchial hyper-responsiveness. IL13 also plays a role in other allergic diseases, such as atopic dermatitis and allergic rhinitis.
Furthermore, studies have shown that IL13 is involved in the pathogenesis of various fibrotic diseases, including pulmonary fibrosis, liver fibrosis, and kidney fibrosis. IL13 promotes tissue remodeling and fibrosis by stimulating the production of extracellular matrix proteins.
IL13 has also been associated with certain types of cancer. It promotes the survival and growth of tumor cells and can contribute to tumor immune evasion. IL13 signaling has been implicated in the progression of glioblastoma, breast cancer, and colorectal cancer, among others.
Application of Human IL13 Protein in Medicine
Given its role in various diseases, targeting IL13 and its signaling pathways has become a potential therapeutic strategy. One approach involves the development of monoclonal antibodies that specifically bind to IL13 or its receptor, blocking its activity. These antibodies can be used to treat asthma and other allergic diseases by reducing inflammation and airway hyper-responsiveness.
In the field of oncology, IL13 has become a target for immunotherapy. Bi-specific antibodies and chimeric antigen receptor (CAR) T-cell therapy targeting IL13 have shown promise in preclinical and early clinical trials for glioblastoma and other solid tumors.
List of Drug Candidates Related to Human IL13 Protein
Several drug candidates targeting IL13 or its signaling have been investigated:
Lebrikizumab: A monoclonal antibody targeting IL13, currently in development for the treatment of asthma and atopic dermatitis.
Tralokinumab: A monoclonal antibody that specifically targets IL13, being studied for the treatment of asthma.
Anrukinzumab: A monoclonal antibody targeting IL13, under investigation for the treatment of idiopathic pulmonary fibrosis.
CAT-354: A monoclonal antibody targeting IL13Rα1, being developed for the treatment of asthma.
AMG 317: A monoclonal antibody that binds to IL4Rα, inhibiting the activity of both IL4 and IL13. It is being investigated for asthma and atopic dermatitis.
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