Dostarlimab API Manufacturers

General Description:

Dostarlimab, identified by CAS number 2022215-59-2, is a notable compound with significant therapeutic applications. Dostarlimab is an IgG₄ humanized monoclonal antibody targeted against the human programmed death receptor-1 (PD-1). PD-1 receptors are found on T-cells and, when activated, serve to inhibit immune responses - some cancers leverage this system by overexpressing PD-1 ligands, thereby effectively inhibiting the anti-tumor immune response that would typically attempt to destroy the cancerous cells. Agents acting on the PD-1 pathway, such as and , facilitate endogenous immune-mediated anti-tumor activity and may therefore be used to treat a wide variety of cancers, including those of the skin, lung, kidneys, and liver. In April 2021, dostarlimab was granted an accelerated approval by the FDA - as GlaxoSmithKline's dostarlimab-gxly (Jemperli) - for the treatment of adult patients with recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer experiencing disease progression despite treatment with platinum-containing chemotherapy regimens. As this accelerated approval was granted only for the treatment of dMMR endometrial cancers, it was approved alongside a companion diagnostic device - the VENTANA MMR RxDx Panel - for use in selecting appropriate patients for treatment. Dostarlimab is currently under investigation for the treatment of rectal cancers with mismatch repair deficiency. A prospective phase II study in patients with mismatch repair-deficient locally advanced rectal cancer resulted in all twelve patients exhibiting a complete clinical response.

Indications:

This drug is primarily indicated for: Dostarlimab-gxly is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Dostarlimab undergoes metabolic processing primarily in: The metabolism of dostarlimab has not been characterized, but it is expected to be degraded via catabolic pathways into smaller peptides and amino acids. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Dostarlimab are crucial for its therapeutic efficacy: During the first cycle, and administered at 500mg intravenously every 3 weeks, the mean C_max and AUC_0-tau of dostarlimab-gxly are 171 mcg/mL and 35,730 mcg.h/mL, respectively. When administered at 1000mg every 6 weeks, the mean C_max and AUC_0-tau are 309 mcg/mL and 95,820 mcg.h/mL, respectively. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Dostarlimab is an important consideration for its dosing schedule: The mean terminal elimination half-life of dostarlimab is 25.4 days. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Dostarlimab is distributed throughout the body with a volume of distribution of: At steady-state, the mean volume of distribution of dostarlimab is 5.3L. This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Dostarlimab is a critical factor in determining its safe and effective dosage: At steady-state, the mean clearance of dostarlimab is 0.007 L/h. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Dostarlimab exerts its therapeutic effects through: Dostarlimab is an immunotherapy that facilitates the body's endogenous anti-tumor immune response in the treatment cancer. It is administered over a span of 30 minutes via intravenous infusion every three to six weeks depending on the cycle. Agents that interfere with the PD-1/PD-L1 pathway, including dostarlimab, remove an important immune system inhibitory response and may therefore induce immune-mediated adverse reactions which can be severe or fatal. These reactions can occur in any organ system and can occur at any time after starting therapy, and while they most often manifest during therapy they may also appear after discontinuing the causative agent. Patients receiving therapy with dostarlimab should be monitored closely for evidence of an underlying immune-mediated reaction and evaluated and treated promptly if an immune-mediated reaction is suspected. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Dostarlimab functions by: Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response. Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Dostarlimab 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:

Dostarlimab is categorized under the following therapeutic classes: Amino Acids, Peptides, and Proteins, Anions, Antibodies, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Antineoplastic and Immunomodulating Agents, Blood Proteins, Electrolytes, Globulins, Hydrogen Sulfide, Immune Checkpoint Inhibitors, Immunoglobulins, Immunoproteins, Ions, MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES, PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors, Programmed Death Receptor-1 Blocking Antibody, Programmed Death Receptor-1-directed Antibody Interactions, Proteins, Serum Globulins, Sulfides, Sulfur Compounds. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Dostarlimab include:

• Molecular Weight: 144000.0
• Molecular Formula: C6420H9832N1680O2014S44