Detailed description page of ThPDB2

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15127 details
Primary information
ID15127
Therapeutic IDTh1568
Protein NameCerliponase alfa
Sequence>Th1568_Cerliponase_alfa SYSPEPDQRRTLPPGWVSLGRADPEEELSLTFALRQQNVERLSELVQAVSDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKWLLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGAEFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFVGGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSVIRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDSDLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIEASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQWLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRVNTELMKAAARGLTLLFASGDSGAGCWSVSGRHQFRPTFPASSPYVTTVGGTSFQEPFLITNEIVDYISGGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYFNASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSASTPVFGGILSLINEHRILSGRPPLGFLNPRLYQQHGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDPVTGWGTPNFPALLKTLLNP
Molecular Weight59
Chemical FormulaNA
Isoelectric PointNA
HydrophobicityNA
Melting pointNA
Half-lifeRefer to FDA Label
DescriptionCerliponase 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).
Indication/DiseaseCerliponase 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 [L755]. 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.
PharmacodynamicsCerliponase 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 ActionThe 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.
ToxicityNo data from carcinogenicity, genotoxicity, and fertility studies. Unwanted effects of cerliponase alfa treatment include pyrexia, ECG abnormalities, decreased CSF protein, seizure and hypersensitivity.
MetabolismPredicted to be metabolized through peptide hydrolysis.
AbsorptionRefer to FDA Label
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) [FDA label].
ClearanceRefer to FDA Label
CategoriesHydrolases
Patents NumberNA
Date of IssueNA
Date of ExpiryNA
Drug InteractionNA
TargetCation-independent mannose-6-phosphate receptor
Brand NameNA
CompanyNA
Brand DescriptionNA
Prescribed ForNA
Chemical NameNA
FormulationNA
Physical Appearance NA
Route of AdministrationNA
Recommended DosageNA
ContraindicationNA
Side EffectsNA
Useful Link 1Link
Useful Link 2NA
RemarksNA