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| 10mg |
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Purity: ≥98%
Sapropterin dihydrochloride [formerly known as Tetrahydrobiopterin (BH4, THB, trade name: Kuvan) or sapropterin] is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4) that is approved for the treatment of BH4 responsive PKU. It is a phenylalanine hydroxylase activator. Sapropterin is a naturally occurring essential cofactor of the three aromatic amino acid hydroxylase enzymes, used in the degradation of amino acid phenylalanine and in the biosynthesis of the neurotransmitters serotonin (5-hydroxytryptamine, 5-HT), melatonin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and is a cofactor for the production of nitric oxide (NO) by the nitric oxide synthases. Chemically, its structure is that of a reduced pteridine derivative.
| ln Vivo |
Hypothesis that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism.[1]
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| Animal Protocol |
sapropterin dihydrochloride was administered by gavage to hyperphenylalaninemic C57BL6-Pahenu2/enu2 mice (Pah−/−) or to wild type C57BL6 mice (Pah+/+) to evaluate the uptake of BH4 into brain and the effect of enteral BH4 administration upon brain monoamine neurotransmitter content. Sapropterin, 100 mg tablets, were dissolved in 1% ascorbic acid immediately prior to administration. The final sapropterin concentration was varied to yield different doses in identical volumes of solution to be administered to the mice. Mice received sapropterin (20, 40, or 100 mg/kg body weight) once daily for four days by gavage. A control group of mice received only 1% ascorbic acid vehicle without added sapropterin. During this period, the animals received standard mouse chow (21% protein by weight) and water ad libitum. On the fifth day, mice were euthanized at various time points following sapropterin administration for tissue harvest. During the time period between sapropterin gavage and euthanasia, mouse chow was withheld in order to minimize variability in blood amino acid concentrations caused by feeding. Animals were sedated using inhaled isoflurane anesthesia. Whole blood was collected by cardiac puncture, allowed to clot in an Eppendorf tube, and serum was separated by centrifugation. The mice were then euthanized by exsanguination and perfused with 20 ml normal saline via the left cardiac ventricle to clear blood from the cerebral circulation. Following decapitation, whole brain was rapidly excised from the cranium, split sagitally, and immediately submerged in liquid nitrogen. Half brains and serum samples were stored at −80°C until processing for amino acid or neurotransmitter analysis.[1]
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| References | |
| Additional Infomation |
Sapropterin dihydrochloride is the dihydrochloride salt of sapropterin. It is used for the diagnosis and treatment of variant forms of phenylketonuria (hyperphenylalaninaemia) associated with tetrahydrobiopterin deficiency. Natural cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and nitric oxide synthetase. It has a role as a diagnostic agent and a coenzyme. It contains a sapropterin.
See also: Sapropterin (has active moiety). Drug Indication Sapropterin Dipharma is indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with phenylketonuria (PKU) who have been shown to be responsive to such treatment. Sapropterin Dipharma is also indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment. Kuvan is indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with phenylketonuria (PKU) who have been shown to be responsive to such treatment. Kuvan is also indicated for the treatment of hyperphenylalaninaemia (HPA) in adults and paediatric patients of all ages with tetrahydrobiopterin (BH4) deficiency who have been shown to be responsive to such treatment. Treatment of hyperphenylalaninemia |
| Molecular Formula |
C9H17CL2N5O3
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|---|---|
| Molecular Weight |
314.17
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| Elemental Analysis |
C, 34.41; H, 5.45; Cl, 22.57; N, 22.29; O, 15.28
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| CAS # |
69056-38-8
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| Related CAS # |
Tetrahydrobiopterin;17528-72-2;Sapropterin;62989-33-7
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| PubChem CID |
135409471
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| Appearance |
White to off-white solid powder
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| Density |
1.9±0.1 g/cm3
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| Boiling Point |
506.6±60.0 °C at 760 mmHg
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| Flash Point |
260.2±32.9 °C
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| Vapour Pressure |
0.0±3.0 mmHg at 25°C
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| Index of Refraction |
1.822
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| LogP |
-4.22
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
19
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| Complexity |
405
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| Defined Atom Stereocenter Count |
3
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| SMILES |
Cl[H].Cl[H].O([H])[C@@]([H])([C@]([H])(C([H])([H])[H])O[H])[C@@]1([H])C([H])([H])N([H])C2=C(C(N([H])C(N([H])[H])=N2)=O)N1[H]
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| Chemical Name |
(6R)-2-Amino-6-((1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride
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| Synonyms |
6R-BH4 dihydrochloride; 6R-Tetrahydro-L-biopterin dihydrochloride; Sapropterin HCl; BioMarin T 1401; Biopten; SN0588; SUN-0588; Tetrahydro-6-biopterin; Dapropterin; Phenoptin; THB; BPH4; 6R-BH4; Tetrahydrobiopterin, sapropterin; trade name Kuvan; Tetrahydrobiopterin Dihydrochloride, R-THBP Dihydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (318.30 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1830 mL | 15.9150 mL | 31.8299 mL | |
| 5 mM | 0.6366 mL | 3.1830 mL | 6.3660 mL | |
| 10 mM | 0.3183 mL | 1.5915 mL | 3.1830 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
PKUDOS: Phenylketonuria (PKU) Demographic, Outcomes, and Safety Registry
CTID: NCT00778206
Phase: Status: Completed
Date: 2022-10-12
Products are for research use only; We do not sell to patients
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