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Synonyms: Kuvan® | sapropterin dihydrochloride | SUN-0588 | T-1401 | tetrahydrobiopterin (THB)
sapropterin is an approved drug (FDA (2007), EMA (2008))
Compound class: Metabolite or derivative
Comment: Sapropterin (also known as tetrahydrobiopterin or BH4) is an essential enzymatic cofactor for aromatic amino acid hydroxylase enzymes; phenylalanine hydroxylase (PAH), tryptophan hydroxylase, tyrosine hydroxylase and for nitric oxide synthase. It is used by PAH to degrade phenylalanine, and is required for the biosynthesis of the neurotransmitters serotonin, melatonin, dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline).
Sapropterin is produced via a pathway of reactions catalysed by the enzymes GTP cyclohydrolase I (GCH1; the primary and rate-limiting reaction), 6-pyruvoyltetrahydropterin synthase (PTPS) and sepiapterin reductase (SR; the terminal reaction).
Ligand Activity Visualisation Charts
These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.✖
|No information available.|
|Summary of Clinical Use|
|This drug is used alongside a low-phenylalanine diet to treat patients with phenylketonuria , as it acts to control blood levels of phenylalanine in some patients. It can also be used to treat dopamine-responsive dystonia which can result from BH4 deficiency (due to defects in the BH4 biosynthetic pathway) and subsequent lack of dopamine biosynthesis.|
|Mechanism Of Action and Pharmacodynamic Effects|
|Phenylalanine hydroxylase (PAH) deficiency causes phenylketonuria (characterised by elevated blood phenylalanine). Supplying additional BH4 (a PAH co-factor) is predicted to optimise residual PAH activity, to bring about a reduction in circulating phenylalanine. Elevated phenylalanine levels are associated with the intellectual and developmental disabilities observed in phenylketonuria patients.
PAH-catalysed conversion of phenylalanine to tyrosine is required for the production of epinephrine (adrenaline) and the synthesis of the neuro-transmitters, serotonin, dopamine, and norepinephrine (noradrenaline). It is also involved in apoptosis and other cellular events mediated by nitric oxide production.
For extended ADME data see the following:
Electronic Medicines Compendium (eMC)
European Medicines Agency (EMA)