Repositioning Candidate Details
| Candidate ID: | R1429 |
| Source ID: | DB12023 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Benralizumab |
| Synonyms: | Benralizumab |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Benralizumab is a humanized recombinant monoclonal antibody of the isotype IgG1k immunoglobulin that specifically binds to the alpha chain of the interleukin 5 receptor (IL-5R) expressed on eosinophils and basophils. It inhibits the binding of IL-5 as well as the hetero-oligomerization of the alpha and beta subunits of the IL-5R, thus blocking, signal transduction. Besides, it is an afucosylated IgG which gives it high affinity for the FcγRIIIα receptor in natural killer cells, macrophages and neutrophils. Benralizumab, FDA approved on November 14, 2017, was developed by MedImmune, the AstraZeneca's global biologic research and development arm. |
| CAS Number: | 1044511-01-4 |
| Molecular Weight: | |
| DrugBank Indication: | Benralizumab is indicated as a maintenance treatment of patients 12 years or older with severe asthma and an eosinophilic phenotype. The pathology of severe asthma with eosinophilic phenotype is also denotated as TH2-high phenotype. The patients with this phenotype are characterized by the expression of IL-5 and IL-13, airway hyperresponsiveness, responsiveness to inhaled corticosteroids, high serum IgE and eosinophilia in blood and airway. In the TH2-high phenotype, IL-5 presents a central role as it is responsible for eosinophil differentiation, survival, activation and migration to the lungs. |
| DrugBank Pharmacology: | Eosinophils are the key target of inflammatory respiratory diseases and they undergo apoptosis in absence of IL-5. Therefore, benralizumab action on the IL-5 receptor in basophils and eosinophils produces the apoptosis and its significant reduction in the blood. On the other hand, Benralizumab binding to natural killer cells FcγRIIIα receptor produces a direct antibody-dependent cell-mediated cytotoxicity. All these effects produce a reduction in eosinophil count in airway mucosa, submucosa, sputum, blood and bone marrow. |
| DrugBank MoA: | Interleukin-5 (IL-5) induces an eosinophil-mediated inflammatory response by binding to the IL-5 receptor (IL-5R) expressed in eosinophils, basophils and some mast cells. Benralizumab, unlike IL-5 low-affinity binding, binds with high affinity to the domain I of the α-chain of IL-5R and blocks its signaling and the proliferation of IL-5-dependent cell lines. On the other hand, Benralizumab is an afucosylated antibody in the CH2 region which gives it a high affinity for the FcγRIIIa on natural killer cells, macrophages and neutrophils. This binding triggers a magnified apoptosis response in eosinophils via antibody-dependent cell-mediated cytotoxicity. |
| Targets: | Interleukin-5 receptor subunit alpha antibody; Low affinity immunoglobulin gamma Fc region receptor III-A binding |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
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| Diseases ID | DO ID | Disease Name | Definition | Class |
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