Cerliponase alfa
Identification
- Summary
Cerliponase alfa is an enzyme replacement therapy used to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency.
- Brand Names
- Brineura
- Generic Name
- Cerliponase alfa
- DrugBank Accession Number
- DB13173
- Background
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).
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Recombinant Enzymes - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 59.0 Da (glycosylated)
- Sequences
>Cerliponase alfa Sequence SYSPEPDQRRTLPPGWVSLGRADPEEELSLTFALRQQNVERLSELVQAVSDPSSPQYGKY LTLENVADLVRPSPLTLHTVQKWLLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGAEFH HYVGGPTETHVVRSPHPYQLPQALAPHVDFVGGLHRFPPTSSLRQRPEPQVTGTVGLHLG VTPSVIRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDSDLAQFMRLFGGNFAHQASVAR VVGQQGRGRAGIEASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQWLMLLSNESALPH VHTVSYGDDEDSLSSAYIQRVNTELMKAAARGLTLLFASGDSGAGCWSVSGRHQFRPTFP ASSPYVTTVGGTSFQEPFLITNEIVDYISGGGFSNVFPRPSYQEEAVTKFLSSSPHLPPS SYFNASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSASTPVFGGILSLINEHRILSGRPP LGFLNPRLYQQHGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLKT LLNP
Download FASTA Format- Synonyms
- Cerliponase alfa
- Immature cell growth-inhibiting gene 1 protein
- Immature human tripeptidyl-peptidase 1
- Immature lysosomal pepstatin-insensitive protease
- Immature tripeptidyl-peptidase I
- External IDs
- BMN 190
- BMN-190
Pharmacology
- Indication
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 4. 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.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Neuronal ceroid lipofuscinosis type 2 •••••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
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.
- Mechanism of action
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.
Target Actions Organism UCation-independent mannose-6-phosphate receptor ligandHumans - Absorption
Refer to FDA Label
- Volume of distribution
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) Label.
- Protein binding
Not Available
- Metabolism
Predicted to be metabolized through peptide hydrolysis.
- Route of elimination
Not Available
- Half-life
Refer to FDA Label
- Clearance
Refer to FDA Label
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
No data from carcinogenicity, genotoxicity, and fertility studies. Unwanted effects of cerliponase alfa treatment include pyrexia, ECG abnormalities, decreased CSF protein, seizure and hypersensitivity.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Brineura Kit 150 mg/5mL Intraventricular BioMarin Pharmaceutical Inc. 2017-04-27 Not applicable US Brineura Injection, solution 150 mg Intracerebral Biomarin International Limited 2020-12-23 Not applicable EU Brineura Solution 150 mg / 5 mL Intracerebral Biomarin International Limited 2019-03-18 Not applicable Canada
Categories
- ATC Codes
- A16AB17 — Cerliponase alfa
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- X8R2D92QP1
- CAS number
- 151662-36-1
References
- General References
- Guhaniyogi J, Sohar I, Das K, Stock AM, Lobel P: Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. J Biol Chem. 2009 Feb 6;284(6):3985-97. doi: 10.1074/jbc.M806943200. Epub 2008 Nov 26. [Article]
- Zhang Y, Chen LY, Han X, Xie W, Kim H, Yang D, Liu D, Songyang Z: Phosphorylation of TPP1 regulates cell cycle-dependent telomerase recruitment. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5457-62. doi: 10.1073/pnas.1217733110. Epub 2013 Mar 18. [Article]
- Pal A, Kraetzner R, Gruene T, Grapp M, Schreiber K, Gronborg M, Urlaub H, Becker S, Asif AR, Gartner J, Sheldrick GM, Steinfeld R: Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. J Biol Chem. 2009 Feb 6;284(6):3976-84. doi: 10.1074/jbc.M806947200. Epub 2008 Nov 26. [Article]
- Intracerebroventricular Cerliponase Alfa (BMN 190) in Children with CLN2 Disease: Interim Results from a Phase 1/2, Open-Label, Dose-Escalation Study [Link]
- External Links
- KEGG Drug
- D10813
- PubChem Substance
- 347911440
- 1922436
- ChEMBL
- CHEMBL3544921
- Wikipedia
- Cerliponase_alfa
- FDA label
- Download (793 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Jansky-Bielschowsky Disease / Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) / Neuronal Ceroid Lipofuscinosis 1 1, 2 Active Not Recruiting Treatment Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1 1, 2 Completed Treatment Jansky-Bielschowsky Disease / Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) / Neuronal Ceroid Lipofuscinosis 2 Not Available Active Not Recruiting Not Available Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1 Not Available Approved for Marketing Not Available Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intracerebral 150 mg Injection, solution Intracerebral; Parenteral 150 MG Kit Intraventricular 150 mg/5mL Solution Intracerebral 150 mg / 5 mL Solution Intracerebral 30 mg - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Ligand
- General Function
- Transporter activity
- Specific Function
- Transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes. Lysosomal enzymes bearing phosphomannosyl residues bind specifically to mannose-6-phosphate r...
- Gene Name
- IGF2R
- Uniprot ID
- P11717
- Uniprot Name
- Cation-independent mannose-6-phosphate receptor
- Molecular Weight
- 274372.42 Da
References
- Meng Y, Sohar I, Wang L, Sleat DE, Lobel P: Systemic administration of tripeptidyl peptidase I in a mouse model of late infantile neuronal ceroid lipofuscinosis: effect of glycan modification. PLoS One. 2012;7(7):e40509. doi: 10.1371/journal.pone.0040509. Epub 2012 Jul 6. [Article]
Drug created at April 28, 2017 19:55 / Updated at June 03, 2022 07:24