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Details

Stereochemistry ABSOLUTE
Molecular Formula C9H15N5O3
Molecular Weight 241.2471
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SAPROPTERIN

SMILES

[H][C@@]1(CNC2=C(N1)C(=O)N=C(N)N2)[C@@H](O)[C@H](C)O

InChI

InChIKey=FNKQXYHWGSIFBK-RPDRRWSUSA-N
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

HIDE SMILES / InChI

Description

Sapropterin dihydrochloride, the active pharmaceutical ingredient in Kuvan Tablets, is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4). Kuvan is indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). Kuvan is to be used in conjunction with a Phe-restricted diet. Kuvan has received orphan drug designation from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA). Kuvan is a synthetic form of BH4, the cofactor for the enzyme phenylalanine hydroxylase (PAH). PAH hydroxylates Phe through an oxidative reaction to form tyrosine. In patients with PKU, PAH activity is absent or deficient. Treatment with BH4 can activate residual PAH enzyme, improve the normal oxidative metabolism of Phe, and decrease Phe levels in some patients.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
KUVAN

Cmax

ValueDoseCo-administeredAnalytePopulation
84.1 ng/mL
10 mg/kg single, oral
SAPROPTERIN plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
559 ng × h/mL
10 mg/kg single, oral
SAPROPTERIN plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
3.67 h
10 mg/kg single, oral
SAPROPTERIN plasma
Homo sapiens

Doses

AEs

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended starting dose is 10 mg/kg/day taken once daily. Response to therapy is determined by change in blood Phe following treatment with drug at 10 mg/kg/day for a period of up to 1 month. Blood Phe levels should be checked after 1 week of treatment and periodically for up to a month. If blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day. Patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment should be discontinued in these patients. Once responsiveness to drug has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. Doses above 20 mg/kg/day have not been evaluated in clinical trials.
Route of Administration: Oral
In Vitro Use Guide
The effect of tetrahydrobiopterin (BH4, SAPROPTERIN) on subunit structure and activity of microsomal and cytosolic Type III nitric oxide synthase (NOS III) was compared. BH4 activates NOS III in the primordial human placenta by promoting its subunit assembly in the membrane, while cytosolic NOS III is relatively insensitive to BH4. Incubation of microsomal membranes with 50 microM final concentration BH4 for 10 min at 37 degrees C resulted in a striking conversion of monomeric NOS III into a protein having the characteristics (electrophoretic mobility, resistance to sodium dodecyl sulphate) of the homodimeric form. In contrast, BH4 induced significantly less marked changes in the NOS III dimer content of cytosolic fractions. Enzyme activity in microsomes is stimulated approximately 6-fold upon addition of 50 microM BH4, while only a 2-fold activation is detectable in cytosolic fractions.