Atoltivimab API Manufacturers

General Description:

Atoltivimab, identified by CAS number 2135632-29-8, is a notable compound with significant therapeutic applications. Ebola virus (EBOV) remains an important human pathogen within the _Ebolavirus_ genus, having been responsible for at least 17 known outbreaks with an average case fatality rate of 43.92%. Immune therapy using monoclonal antibodies (mAbs) is becoming an increasingly attractive therapeutic method to combat infectious diseases due to its rapid development, low toxicity, and high specificity. The chief surface target of EBOV particles is the GP_1,2 glycoprotein, which also appears on the surface of EBOV-infected cells, offering opportunities for both neutralizing and cytotoxic (i.e. through Fc-mediated immune effector function) antibody effects to play a role in combatting EBOV infection. A recent large-scale study elucidated that both neutralizing and Fc-mediated functions of antibodies were important for therapeutic benefit in animal models of EBOV infection. INMAZEB™, formerly referred to as REGN-EB3, combines the three humanized IgG1κ mAbs Atoltivimab (REGN 3470), (REGN 3471), and (REGN 3479) in equimolar proportions. All three mAbs bind to a distinct portion of the GP_1,2 glycoprotein and collectively provide neutralizing and Fc-mediated immune effector function against EBOV _in vitro_ and protection against EBOV infection _in vivo_. INMAZEB™ is produced by Regeneron Pharmaceuticals and was granted FDA approval on October 14, 2020.

Indications:

This drug is primarily indicated for: Atoltivimab is indicated in combination with and for the treatment of _Zaire ebolavirus_ infection in adult and pediatric patients, including neonates born to a mother who has been confirmed positive by RT-PCR for _Zaire ebolavirus_ infection. This combination has not been established as efficacious for any other species within either the _Ebolavirus_ or _Marburgvirus_ genera; special care should be taken to evaluate the susceptibility of circulating _Zaire ebolavirus_ strains before beginning treatment, and the possible emergence of resistance should be monitored. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Absorption:

The absorption characteristics of Atoltivimab are crucial for its therapeutic efficacy: Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean C_max of 1220 ± 101 mg/L and a mean AUC_0-∞ of 17,100 ± 4480 mg\*day/L. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Atoltivimab is an important consideration for its dosing schedule: Atoltivimab administered to healthy subjects at 50 mg/kg has a mean elimination half-life of 21.2 ± 3.36 days. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Atoltivimab is distributed throughout the body with a volume of distribution of: Atoltivimab administered to healthy subjects at 50 mg/kg produced a mean steady-state volume of distribution of 58.2 ± 2.66 mL/kg. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Atoltivimab is a critical factor in determining its safe and effective dosage: Atoltivimab administered to healthy subjects at 50 mg/kg has a mean clearance of 3.08 ± 0.719 mL/day/kg. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Atoltivimab exerts its therapeutic effects through: Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the GP_1,2 glycoprotein that provides both neutralizing and Fc-dependent immune-mediated activity against _Zaire ebolavirus_. As a mAb, Atoltivimab exhibits low toxicity and is generally well tolerated but does include the risk of potentially life-threatening hypersensitivity reactions. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Atoltivimab functions by: Ebola virus (EBOV) is one of several viruses within the _Ebolavirus_ genus known to infect humans with an average case fatality rate of 43.92%. EBOV particles expose the GP_1,2 glycoprotein on their surface, which comprises a trimer of GP₁ and GP₂ subunit heterodimers, with the subunits connected by a disulfide bond. GP_1,2 plays an important role in both cell surface attachment/entry and eventual lysosomal escape through binding to the NPC intracellular cholesterol transporter 1/Niemann-Pick C1 protein (NPC1). In this manner, GP_1,2 is integral to the pathogenic cycle of EBOV. Atoltivimab is a fully-humanized IgG1κ monoclonal antibody (mAb) directed against the EBOV GP_1,2 glycoprotein, which binds the GP_1,2 glycan cap parallel to the viral surface with a binding affinity (_K_D_) of between 7.74 and 7.84 nM. Atoltivimab exhibits strong (<90%) neutralization of chimeric lentiviral particles expressing EBOV GP_1,2 with a half-maximal inhibitory concentration (IC₅₀) value of 0.27 nM. In addition, Atoltivimab is capable of dose-dependent activation of FcγRIIIa signalling in effector cells in the presence of GP_1,2-expressing cells with a half-maximal effective concentration (EC₅₀) of 2.9 nM. Combined with and , Atoltivimab works to block EBOV cell infection and lysosomal escape, as well as the potential antibody-dependent cell-mediated killing of EBOV-infected cells. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Classification:

Atoltivimab 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:

Atoltivimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anti-Infective Agents, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antiviral Agents, Blood Proteins, Globulins, Immunoglobulins, Immunoproteins, Proteins, Serum Globulins, Treatments for Ebola Virus Disease. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Atoltivimab include:

• Molecular Weight: 145097.54
• Molecular Formula: C6448H9954N1726O2002S44