sapropterin   Click here for help

GtoPdb Ligand ID: 5276

Synonyms: Kuvan® | sapropterin dihydrochloride | SUN-0588 | T-1401 | tetrahydrobiopterin (THB)
Approved drug PDB Ligand Immunopharmacology Ligand
sapropterin is an approved drug (FDA (2007), EMA (2008))
Compound class: Metabolite
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).
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
Hydrogen bond acceptors 7
Hydrogen bond donors 6
Rotatable bonds 2
Topological polar surface area 136.29
Molecular weight 241.12
XLogP -0.1
No. Lipinski's rules broken 1
Click here for help
Canonical SMILES CC(C(C1CNc2c(N1)c(=O)[nH]c(n2)N)O)O
Isomeric SMILES C[C@@H]([C@@H]([C@H]1CNc2c(N1)c(=O)[nH]c(n2)N)O)O
InChI InChI=1S/C9H15N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17)/t3-,4+,6-/m0/s1
No information available.
Summary of Clinical Use Click here for help
This drug is used alongside a low-phenylalanine diet to treat patients with phenylketonuria [1], 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 Click here for help
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.
External links Click here for help