Tetrahydrobiopterin

Tetrahydrobiopterin
INN: Sapropterin
Clinical data
Trade namesKuvan, Biopten
Other namesSapropterin hydrochloride (JAN JP), Sapropterin dihydrochloride (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa608020
License data
Pregnancy
category
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life4 hours (healthy adults)
6–7 hours (PKU patients)
Identifiers
IUPAC name
  • (6R)-2-Amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(1H)-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.164.121
Chemical and physical data
FormulaC9H15N5O3
Molar mass241.251 g·mol−1
3D model (JSmol)
SMILES
  • CC(C(C1CNC2=C(N1)C(=O)N=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 Y
  • Key:FNKQXYHWGSIFBK-RPDRRWSUSA-N Y
 NY (what is this?)  (verify)

Tetrahydrobiopterin (BH4, THB), also known as sapropterin (INN),[5][6] is a cofactor of the three aromatic amino acid hydroxylase enzymes,[7] used in the metabolism 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.[8][9] Chemically, its structure is that of a (dihydropteridine reductase) reduced pteridine derivative (quinonoid dihydrobiopterin).[10]

Tetrahydrobiopterin is available as a tablet for oral administration in the form of sapropterin dihydrochloride (BH4*2HCL).[11][3][4] It was approved for use in the United States as a tablet in December 2007[12][13] and as a powder in December 2013.[14][13] It was approved for use in the European Union in December 2008,[4] Canada in April 2010,[2] and Japan in July 2008.[13] It is sold under the brand names Kuvan and Biopten.[4][3][13] The typical cost of treating a patient with Kuvan is US$100,000 per year.[15] BioMarin holds the patent for Kuvan until at least 2024, but Par Pharmaceutical has a right to produce a generic version by 2020.[16]

  1. ^ "Sapropterin (Kuvan) Use During Pregnancy". Drugs.com. 17 May 2019. Retrieved 4 March 2020.
  2. ^ a b "Kuvan Product information". Health Canada. 25 April 2012. Retrieved 24 June 2022.
  3. ^ a b c "Kuvan- sapropterin dihydrochloride tablet Kuvan- sapropterin dihydrochloride powder, for solution Kuvan- sapropterin dihydrochloride powder, for solution". DailyMed. 13 December 2019. Retrieved 4 March 2020.
  4. ^ a b c d "Kuvan EPAR". European Medicines Agency (EMA). 4 March 2020. Retrieved 4 March 2020.
  5. ^ "Sapropterin". Drugs.com. 28 February 2020. Retrieved 4 March 2020.
  6. ^ "International Non-proprietary Names for Pharmaceutical Substances (INN)". Fimea. Archived from the original on 1 October 2020. Retrieved 4 March 2020.
  7. ^ Kappock TJ, Caradonna JP (November 1996). "Pterin-Dependent Amino Acid Hydroxylases". Chemical Reviews. 96 (7): 2659–2756. doi:10.1021/CR9402034. PMID 11848840.
  8. ^ Cavaleri et al. Blood concentrations of neopterin and biopterin in subjects with depression: A systematic review and meta-analysis Progress in Neuro-Psychopharmacology and Biological Psychiatry 2023. 120:110633. http://dx.doi.org/10.1016/j.pnpbp.2022.110633
  9. ^ Całka J (2006). "The role of nitric oxide in the hypothalamic control of LHRH and oxytocin release, sexual behavior and aging of the LHRH and oxytocin neurons". Folia Histochemica et Cytobiologica. 44 (1): 3–12. PMID 16584085.
  10. ^ Bhagavan NV (2015). Essentials of Medical Biochemistry With Clinical Cases, 2nd Edition. USA: Elsevier. p. 256. ISBN 978-0-12-416687-5.
  11. ^ Schaub J, Däumling S, Curtius HC, Niederwieser A, Bartholomé K, Viscontini M, et al. (August 1978). "Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis". Archives of Disease in Childhood. 53 (8): 674–6. doi:10.1136/adc.53.8.674. PMC 1545051. PMID 708106.
  12. ^ "Drug Approval Package: Kuvan (Sapropterin Dihydrochloride) NDA #022181". U.S. Food and Drug Administration (FDA). 24 March 2008. Retrieved 4 March 2020.
  13. ^ a b c d "Kuvan (sapropterin dihydrochloride) Tablets and Powder for Oral Solution for PKU". BioMarin. Archived from the original on 4 March 2020. Retrieved 4 March 2020.
  14. ^ "Drug Approval Package: Kuvan Powder for Oral Solution (Sapropterin Dihydrochloride) NDA #205065". U.S. Food and Drug Administration (FDA). 28 February 2014. Retrieved 4 March 2020.
  15. ^ Herper M (28 July 2016). "How Focusing On Obscure Diseases Made BioMarin A $15 Billion Company". Forbes. Retrieved 9 October 2017.
  16. ^ "BioMarin Announces Kuvan (sapropterin dihydrochloride) Patent Challenge Settlement". BioMarin Pharmaceutical Inc. 13 April 2017. Retrieved 9 October 2017 – via PR Newswire.
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