pabinafusp alfa 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
fusion proteins	5488	2140211-48-7

Description:

Molecule	Description
Molfile Synonyms: pabinafusp alfa pabinafusp alfa (genetical recombination) izcargo JR-141	Pabinafusp alfa is a fusion protein consisting of a humanized anti-hTfR antibody and hIDS. The humanized anti-hTfR antibody is considered to bind to TfRs expressed in the luminal cell membrane of brain microvascular endothelial cells composing the blood-brain barrier, being transported together with the TfR, passing through brain microvascular endothelial cells via transcytosis (which involves the mechanisms of uptake into the cell via endocytosis and release outside the cell via exocytosis) and further penetrating the basal lamina into neuronal cells in the brain parenchyma. In addition, after binding of pabinafusp alfa to M6PR on the cell membrane and cellular uptake via endocytosis, newly formed endosomes are thought to fuse with lysosomes and move into them. In patients with MPS, the type of accumulating GAG differs depending on the MPS phenotype, and CNS symptoms develops in patients with MPS phenotypes that are associated with the accumulation of HS. HS concentrations in CSF are high in patients with MPS-II who have intellectual disability, compared with those who do not have intellectual disability. These findings and other factors have suggested that HS plays a vital role in the development of CNS symptoms. The hIDS of pabinafusp alfa is considered to promote the degradation of HS in the brain parenchyma, thereby suppressing the development or progression of CNS symptoms. It has been demonstrated that pabinafusp alfa has binding affinity for M6PR and hTfR, and is taken up by human fibroblasts via the receptors. Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Molfile

Synonyms:

pabinafusp alfa
pabinafusp alfa (genetical recombination)
izcargo
JR-141

Pabinafusp alfa is a fusion protein consisting of a humanized anti-hTfR antibody and hIDS. The humanized anti-hTfR antibody is considered to bind to TfRs expressed in the luminal cell membrane of brain microvascular endothelial cells composing the blood-brain barrier, being transported together with the TfR, passing through brain microvascular endothelial cells via transcytosis (which involves the mechanisms of uptake into the cell via endocytosis and release outside the cell via exocytosis) and further penetrating the basal lamina into neuronal cells in the brain parenchyma. In addition, after binding of pabinafusp alfa to M6PR on the cell membrane and cellular uptake via endocytosis, newly formed endosomes are thought to fuse with lysosomes and move into them. In patients with MPS, the type of accumulating GAG differs depending on the MPS phenotype, and CNS symptoms develops in patients with MPS phenotypes that are associated with the accumulation of HS. HS concentrations in CSF are high in patients with MPS-II who have intellectual disability, compared with those who do not have intellectual disability. These findings and other factors have suggested that HS plays a vital role in the development of CNS symptoms. The hIDS of pabinafusp alfa is considered to promote the degradation of HS in the brain parenchyma, thereby suppressing the development or progression of CNS symptoms. It has been demonstrated that pabinafusp alfa has binding affinity for M6PR and hTfR, and is taken up by human fibroblasts via the receptors.

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

None

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
March 23, 2021	PMDA	JCR Pharmaceuticals Co., Ltd.

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

None

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

None

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Mucopolysaccharidosis type II	indication	70737009	DOID:12799

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Type	Activity value (-log[M])	Bioact source	MoA source
IgG receptor FcRn large subunit p51	Membrane receptor	P55899	FCGRN_HUMAN	Kd	5.74	DRUG LABEL	DRUG LABEL
Transferrin receptor protein 1	Membrane receptor	P02786	TFR1_HUMAN	Kd	9.91	DRUG LABEL	DRUG LABEL
Cation-independent mannose-6-phosphate receptor	Membrane receptor	P11717	MPRI_HUMAN	Kd	8.04	DRUG LABEL	DRUG LABEL

External reference:

ID	Source
CHEMBL4594565	ChEMBL_ID
11772	IUPHAR_LIGAND_ID
DB15633	DRUGBANK_ID
D11812	KEGG_DRUG
C5242456	UMLSCUI
10995	INN_ID
TRF8S0U6ON	UNII

Pharmaceutical products:

None