Cerliponase alfa API Manufacturers

General Description:

Cerliponase alfa, identified by CAS number 151662-36-1, is a notable compound with significant therapeutic applications. Cerliponase alfa is an enzyme replacement treatment for a specific form of Batten disease. It was the first FDA-approved treatment to slow loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. Intraventricular administration of the drug allows significant uptake into the brain. Cerliponase alfa was approved in April, 2017 (as Brineura).

Indications:

This drug is primarily indicated for: Cerliponase alfa is a treatment for late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease to decelerate the progressive motor function decline in patients 3 years of age and older. CLN2 disease is a form of Batten disease, a rare inherited neurodegenerative disorder and is associated with seizures, ataxia, rapid loss of language and motor functions, blindness, and early death . It is caused by the lack the lysosomal enzyme tripeptidyl peptidase-1 (TPP1) and subsequent accumulation of lysosomal storage materials normally metabolized by this enzyme in the central nervous system. Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Cerliponase alfa undergoes metabolic processing primarily in: Predicted to be metabolized through peptide hydrolysis. This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Cerliponase alfa are crucial for its therapeutic efficacy: Refer to FDA Label. The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Cerliponase alfa is an important consideration for its dosing schedule: Refer to FDA Label. This determines the duration of action and helps in formulating effective dosing regimens.

Volume of Distribution:

Cerliponase alfa is distributed throughout the body with a volume of distribution of: The estimated CSF volume of distribution of cerliponase alfa following intraventricular infusion of 300mg of Brineura (median Vss = 245 mL) exceeds the typical CSF volume (100 mL) . This metric indicates how extensively the drug permeates into body tissues.

Clearance:

The clearance rate of Cerliponase alfa is a critical factor in determining its safe and effective dosage: Refer to FDA Label. It reflects the efficiency with which the drug is removed from the systemic circulation.

Pharmacodynamics:

Cerliponase alfa exerts its therapeutic effects through: Cerliponase alfa contains the active substance tripeptidyl peptidase-1 (rhTPP1), a recombinant human lysosomal exopeptidase which cleaves the N-terminal of tripeptides with a broad substrate specificity. Cerliponase alfa slows the progressive decline in motor function caused by abnormal motor signalling in the brain by restoring the normal levels and activity of TPP1. The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Cerliponase alfa functions by: The mature form of enzyme contains 5 consensus N-glycosylation sites with high mannose, phosphorylated high mannose and complex glycosylation structures. It is taken up by LINCL fibroblasts and translocated to the lysosomes through the Cation Independent Mannose-6-Phosphate Receptor (CI-MPR, also known as M6P/IGF2 receptor). Cerliponase alfa is activated in the lysosome under low pH conditions and the activated proteolytic form of rhTPP1 cleaves tripeptides from the N-terminus of stored proteins. This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Classification:

Cerliponase alfa 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:

Cerliponase alfa is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Amino Acids, Peptides, and Proteins, Enzymes, Enzymes and Coenzymes, Exopeptidases, Hydrolases, Hydrolytic Lysosomal N-terminal Tripeptidyl Peptidase, Peptide Hydrolases, Proteins. These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Cerliponase alfa include:

• Molecular Weight: 59.0