Benralizumab API Manufacturers

General Description:

Benralizumab, identified by CAS number 1044511-01-4, is a notable compound with significant therapeutic applications. 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.

Indications:

This drug is primarily indicated for: 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. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Benralizumab undergoes metabolic processing primarily in: As any monoclonal IgG antibody, Beralizumab is degraded by proteases widely spread in the body. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Benralizumab are crucial for its therapeutic efficacy: Subcutaneous administration of Benralizumab presented a dose-proportional pharmacokinetic profile. The administration of 20-200 mg presented an absorption half-life of 3.6 days with a bioavailability of 58%. It is also reported for Benralizumab a Cmax of 82 mcg/ml and AUC of 775 mcg day/ml. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Benralizumab is an important consideration for its dosing schedule: The half-life of Benralizumab is estimated to be 15-18 days. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Benralizumab exhibits a strong affinity for binding with plasma proteins: There is no reports indicating that Benralizumab binds to plasma proteins. This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Benralizumab from the body primarily occurs through: Benraluzimab presents a linear pharmacokinetic without target-receptor mediated clearance. The presence of a dose-proportional pharmacokinetics suggests a rapid depletion of the target and an elimination mainly mediated through the reticuloendothelial system. Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Benralizumab is distributed throughout the body with a volume of distribution of: Pharmacokinetic reports of Benralizumab showed a volume of distribution in a range of 52-93ml/kg. For a 70kg individual, the central volume of distribution of Benralizumab is 3.2 L while the peripheral volume of distribution is reported to be 2.5 L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Benralizumab is a critical factor in determining its safe and effective dosage: For a subject weighting 70kg, the typical systemic clearance is 0.29L/day. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Benralizumab exerts its therapeutic effects through: 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. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Benralizumab functions by: 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. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Benralizumab belongs to the None, classified under the direct parent group Peptides. This compound is a part of the Organic Compounds, falling under the Organic Acids superclass, and categorized within the Carboxylic Acids and Derivatives class, specifically within the Amino Acids, Peptides, and Analogues subclass.

Categories:

Benralizumab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anti-Asthmatic Agents, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Blood Proteins, Drugs for Obstructive Airway Diseases, Globulins, Immunoglobulins, Immunoproteins, Interleukin 5 Receptor alpha-directed Antibody Interactions, Interleukin Antagonists, Interleukin-5 Receptor alpha-directed Cytolytic Antibody, Proteins, Respiratory System Agents, Serum Globulins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Benralizumab include:

• Melting Point: 69 °C (midpoint transition), 80 °C (whole IgG1)
• Isoelectric Point: 6.6 - 7.2
• Molecular Weight: 146054.0
• Molecular Formula: C6492H10060N1724O2028S42