Sapropterin HCl
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MedKoo CAT#: 330141

CAS#: 69056-38-8 (HCl)

Description: Sapropterin, also known as Tetrahydrobiopterin (BH4, THB, trade name Kuvan) or sapropterin (INN) 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.

Chemical Structure

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Sapropterin HCl
CAS# 69056-38-8 (HCl)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 330141
Name: Sapropterin HCl
CAS#: 69056-38-8 (HCl)
Chemical Formula: C9H17Cl2N5O3
Exact Mass: 0.00
Molecular Weight: 314.170
Elemental Analysis: C, 34.41; H, 5.45; Cl, 22.57; N, 22.29; O, 15.28

Price and Availability

Size Price Availability Quantity
100mg USD 350 2 Weeks
250mg USD 550 2 Weeks
500mg USD 1250 2 Weeks
1g USD 1950 2 Weeks
5g USD 6250 2 Weeks
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Related CAS #: 62989-33-7 (free base)   69056-38-8 (HCl)   90366-07-7 (sesqui HCl)   17528-72-2 (free base),  

Synonym: Sapropterin HCl; BioMarin T 1401; Biopten; SN0588; SUN-0588; Tetrahydro-6-biopterin; Dapropterin; Phenoptin; THB; BPH4; 6R-BH4; Tetrahydrobiopterin, sapropterin; trade name Kuvan.

IUPAC/Chemical Name: (6R)-2-Amino-6-((1R,2S)-1,2-dihydroxypropyl)-5,6,7,8-tetrahydro-4(1H)-pteridinone dihydrochloride

InChi Key: RKSUYBCOVNCALL-NTVURLEBSA-N

InChi Code: InChI=1S/C9H15N5O3.2ClH/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);2*1H/t3-,4+,6-;;/m0../s1

SMILES Code: O=C1N=C(N)NC2=C1N[C@@H]([C@@H](O)[C@@H](O)C)CN2.[H]Cl.[H]Cl

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Product Data
Instruction:
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Biological target: Sapropterin HCl is a cofactor that facilitates the production of aromatic amino acids, neurotransmitters, and nitric oxide when bound to specific enzymes. Sapropterin HCl acts as a radical-trapping antioxidant, inhibiting phospholipid oxidation in lipid membranes. Sapropterin HCl inhibits ferroptosis in various cell types, such as IKE- or RSL3-induced ferroptosis in HT-1080 cells (EC50 = 21 and 69 µM) and ferroptosis induced by the knockout of glutathione peroxidase (Gpx4-/-) in immortalized mouse fibroblasts. It reduces RLS3-induced lipid peroxidation in murine fibroblasts and HT-1080 cells when used at a concentration of 50 µM.
In vitro activity: In vitro, the study investigated the transport of sapropterin across the plasma membrane. Sapropterin supplementation is used to address Sapropterin deficiencies, although its rapid clearance presents challenges. This research identified hENT2 as a key transporter for precursor pterins, such as sepiapterin, BH(2), and sapropterin, impacting intracellular BH(2)/sapropterin ratios. Reference: Mol Genet Metab. 2011 Jan;102(1):18-28. https://pubmed.ncbi.nlm.nih.gov/20956085/
In vivo activity: The study suggests that sapropterin may exacerbate autoimmune CNS diseases, with lipid disruptions playing a mechanistic role. Mice with immunization-induced autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, were treated with sapropterin. The results indicated that sapropterin treatment led to higher EAE disease scores and increased T-cell infiltration in the spinal cord. This was associated with changes in lipid profiles known to disrupt the blood-brain barrier in EAE mice. Reference: Neurotherapeutics. 2021 Jul;18(3):1862-1879. https://pubmed.ncbi.nlm.nih.gov/33844153/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Water 100.0 318.30

Preparing Stock Solutions

The following data is based on the product molecular weight 314.17 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ohashi A, Sugawara Y, Mamada K, Harada Y, Sumi T, Anzai N, Aizawa S, Hasegawa H. Membrane transport of sepiapterin and dihydrobiopterin by equilibrative nucleoside transporters: a plausible gateway for the salvage pathway of tetrahydrobiopterin biosynthesis. Mol Genet Metab. 2011 Jan;102(1):18-28. doi: 10.1016/j.ymgme.2010.09.005. Epub 2010 Sep 18. PMID: 20956085. 2. Kamada Y, Jenkins GJ, Lau M, Dunbar AY, Lowe ER, Osawa Y. Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 2005 Dec 7;142(1):19-27. doi: 10.1016/j.molbrainres.2005.09.003. Epub 2005 Oct 10. PMID: 16216381. 3. Schmitz K, Trautmann S, Hahnefeld L, Fischer C, Schreiber Y, Wilken-Schmitz A, Gurke R, Brunkhorst R, Werner ER, Watschinger K, Wicker S, Thomas D, Geisslinger G, Tegeder I. Sapropterin (BH4) Aggravates Autoimmune Encephalomyelitis in Mice. Neurotherapeutics. 2021 Jul;18(3):1862-1879. doi: 10.1007/s13311-021-01043-4. Epub 2021 Apr 12. PMID: 33844153; PMCID: PMC8609075. 4. Engineer A, Lim YJ, Lu X, Kim MY, Norozi K, Feng Q. Sapropterin reduces coronary artery malformation in offspring of pregestational diabetes mice. Nitric Oxide. 2020 Jan 1;94:9-18. doi: 10.1016/j.niox.2019.10.002. Epub 2019 Oct 7. PMID: 31600600.
In vitro protocol: 1. Ohashi A, Sugawara Y, Mamada K, Harada Y, Sumi T, Anzai N, Aizawa S, Hasegawa H. Membrane transport of sepiapterin and dihydrobiopterin by equilibrative nucleoside transporters: a plausible gateway for the salvage pathway of tetrahydrobiopterin biosynthesis. Mol Genet Metab. 2011 Jan;102(1):18-28. doi: 10.1016/j.ymgme.2010.09.005. Epub 2010 Sep 18. PMID: 20956085. 2. Kamada Y, Jenkins GJ, Lau M, Dunbar AY, Lowe ER, Osawa Y. Tetrahydrobiopterin depletion and ubiquitylation of neuronal nitric oxide synthase. Brain Res Mol Brain Res. 2005 Dec 7;142(1):19-27. doi: 10.1016/j.molbrainres.2005.09.003. Epub 2005 Oct 10. PMID: 16216381.
In vivo protocol: 1. Schmitz K, Trautmann S, Hahnefeld L, Fischer C, Schreiber Y, Wilken-Schmitz A, Gurke R, Brunkhorst R, Werner ER, Watschinger K, Wicker S, Thomas D, Geisslinger G, Tegeder I. Sapropterin (BH4) Aggravates Autoimmune Encephalomyelitis in Mice. Neurotherapeutics. 2021 Jul;18(3):1862-1879. doi: 10.1007/s13311-021-01043-4. Epub 2021 Apr 12. PMID: 33844153; PMCID: PMC8609075. 2. Engineer A, Lim YJ, Lu X, Kim MY, Norozi K, Feng Q. Sapropterin reduces coronary artery malformation in offspring of pregestational diabetes mice. Nitric Oxide. 2020 Jan 1;94:9-18. doi: 10.1016/j.niox.2019.10.002. Epub 2019 Oct 7. PMID: 31600600.

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1: Doyle S, O'Regan M, Stenson C, Bracken J, Hendroff U, Agasarova A, Deverell D, Treacy EP. Extended Experience of Lower Dose Sapropterin in Irish Adults with Mild Phenylketonuria. JIMD Rep. 2017 Oct 14. doi: 10.1007/8904_2017_63. [Epub ahead of print] PubMed PMID: 29030855.

2: Kör D, Yılmaz BŞ, Bulut FD, Ceylaner S, Mungan NÖ. Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose. J Pediatr Endocrinol Metab. 2017 Jul 26;30(7):713-718. doi: 10.1515/jpem-2016-0461. PubMed PMID: 28593914.

3: Muntau AC, Burlina A, Eyskens F, Freisinger P, De Laet C, Leuzzi V, Rutsch F, Sivri HS, Vijay S, Bal MO, Gramer G, Pazdírková R, Cleary M, Lotz-Havla AS, Munafo A, Mould DR, Moreau-Stucker F, Rogoff D. Efficacy, safety and population pharmacokinetics of sapropterin in PKU patients <4 years: results from the SPARK open-label, multicentre, randomized phase IIIb trial. Orphanet J Rare Dis. 2017 Mar 9;12(1):47. doi: 10.1186/s13023-017-0600-x. PubMed PMID: 28274234; PubMed Central PMCID: PMC5343543.

4: Hawks Z, Shimony J, Rutlin J, Grange DK, Christ SE, White DA. Pretreatment cognitive and neural differences between sapropterin dihydrochloride responders and non-responders with phenylketonuria. Mol Genet Metab Rep. 2017 Feb 23;12:8-13. doi: 10.1016/j.ymgmr.2017.01.013. eCollection 2017 Sep. PubMed PMID: 28271047; PubMed Central PMCID: PMC5323508.

5: Feldmann R, Wolfgart E, Weglage J, Rutsch F. Sapropterin treatment does not enhance the health-related quality of life of patients with phenylketonuria and their parents. Acta Paediatr. 2017 Jun;106(6):953-959. doi: 10.1111/apa.13799. Epub 2017 Mar 19. PubMed PMID: 28235150.

6: Yildiz Y, Dursun A, Tokatli A, Coskun T, Sivri S. Partial hydatidiform mole in a phenylketonuria patient treated with sapropterin dihydrochloride. Gynecol Endocrinol. 2017 Jan;33(1):19-20. doi: 10.1080/09513590.2016.1247796. Epub 2016 Nov 29. PubMed PMID: 27898272.

7: Fluegge K. A reply to 'Metabolic effects of sapropterin treatment in autism spectrum disorder: a preliminary study'. Transl Psychiatry. 2016 Apr 26;6:e793. doi: 10.1038/tp.2016.24. PubMed PMID: 27115124; PubMed Central PMCID: PMC4872393.

8: Tansek MZ, Groselj U, Kelvisar M, Kobe H, Lampret BR, Battelino T. Long-term BH4 (sapropterin) treatment of children with hyperphenylalaninemia - effect on median Phe/Tyr ratios. J Pediatr Endocrinol Metab. 2016 May 1;29(5):561-6. doi: 10.1515/jpem-2015-0337. PubMed PMID: 26910740.

9: Ünal Ö, Gökmen-Özel H, Coşkun T, Özgül RK, Yücel D, Hişmi B, Tokatlı A, Dursun A, Sivri HS. Sapropterin dihydrochloride treatment in Turkish hyperphenylalaninemic patients under age four. Turk J Pediatr. 2015 May-Jun;57(3):213-8. PubMed PMID: 26701937.

10: Winn SR, Scherer T, Thöny B, Harding CO. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU). Mol Genet Metab. 2016 Jan;117(1):5-11. doi: 10.1016/j.ymgme.2015.11.012. Epub 2015 Nov 26. PubMed PMID: 26653793; PubMed Central PMCID: PMC4706464.

11: Reverter E, Mesonero F, Seijo S, Martínez J, Abraldes JG, Peñas B, Berzigotti A, Deulofeu R, Bosch J, Albillos A, García-Pagán JC. Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients With Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo-Controlled Study. Am J Gastroenterol. 2015 Jul;110(7):985-92. doi: 10.1038/ajg.2015.185. Epub 2015 Jun 16. PubMed PMID: 26077176.

12: Trefz FK, Muntau AC, Lagler FB, Moreau F, Alm J, Burlina A, Rutsch F, Bélanger-Quintana A, Feillet F; KAMPER investigators. The Kuvan(®) Adult Maternal Paediatric European Registry (KAMPER) Multinational Observational Study: Baseline and 1-Year Data in Phenylketonuria Patients Responsive to Sapropterin. JIMD Rep. 2015;23:35-43. doi: 10.1007/8904_2015_425. Epub 2015 Mar 31. PubMed PMID: 25822821; PubMed Central PMCID: PMC4484899.

13: Somaraju UR, Merrin M. Sapropterin dihydrochloride for phenylketonuria. Cochrane Database Syst Rev. 2015 Mar 27;(3):CD008005. doi: 10.1002/14651858.CD008005.pub4. Review. PubMed PMID: 25812600.

14: Longo N, Arnold GL, Pridjian G, Enns GM, Ficicioglu C, Parker S, Cohen-Pfeffer JL; Phenylketonuria Demographics, Outcomes and Safety Registry. Long-term safety and efficacy of sapropterin: the PKUDOS registry experience. Mol Genet Metab. 2015 Apr;114(4):557-63. doi: 10.1016/j.ymgme.2015.02.003. Epub 2015 Feb 16. PubMed PMID: 25724073.

15: Bushueva TV, Kuzenkova LM, Borovik TÉ, Nazarenko LP, Seitova GN, Filimonova MN, Pichkur NA, Samonenko NV, Shkurko TA, Akhmadeeva ÉN, Mardanova AK, Garifullina ÉR, Kovtun OP, Bazhenova IuL, Alimova IL, Kostiakova EA, Minaĭcheva LI, Saliukova OA, Sivokha VM, Rozenson OL. [Open, non-comparative phase III clinical study to evaluate the efficacy and safety of sapropterin in patients with phenylketonuria and hyperphenylalaninemia]. Vestn Ross Akad Med Nauk. 2014;(7-8):69-77. Russian. PubMed PMID: 25563006.

16: Burton B, Grant M, Feigenbaum A, Singh R, Hendren R, Siriwardena K, Phillips J 3rd, Sanchez-Valle A, Waisbren S, Gillis J, Prasad S, Merilainen M, Lang W, Zhang C, Yu S, Stahl S. A randomized, placebo-controlled, double-blind study of sapropterin to treat ADHD symptoms and executive function impairment in children and adults with sapropterin-responsive phenylketonuria. Mol Genet Metab. 2015 Mar;114(3):415-24. doi: 10.1016/j.ymgme.2014.11.011. Epub 2014 Nov 26. PubMed PMID: 25533024.

17: Stockler-Ipsiroglu S, Yuskiv N, Salvarinova R, Apatean D, Ho G, Cheng B, Giezen A, Lillquist Y, Ueda K. Individualized long-term outcomes in blood phenylalanine concentrations and dietary phenylalanine tolerance in 11 patients with primary phenylalanine hydroxylase (PAH) deficiency treated with Sapropterin-dihydrochloride. Mol Genet Metab. 2015 Mar;114(3):409-14. doi: 10.1016/j.ymgme.2014.11.014. Epub 2014 Dec 3. PubMed PMID: 25497838.

18: Jurecki ER, Cunningham A, Mahoney JJ, Tingley D, Chung S, James N, Cohen-Pfeffer JL. Sapropterin Dihydrochloride Mixed With Common Foods and Beverages. Top Clin Nutr. 2014 Oct;29(4):325-331. PubMed PMID: 25382934; PubMed Central PMCID: PMC4213132.

19: Qi Y, Mould DR, Zhou H, Merilainen M, Musson DG. A prospective population pharmacokinetic analysis of sapropterin dihydrochloride in infants and young children with phenylketonuria. Clin Pharmacokinet. 2015 Feb;54(2):195-207. doi: 10.1007/s40262-014-0196-4. PubMed PMID: 25338975; PubMed Central PMCID: PMC4306193.

20: Longo N, Siriwardena K, Feigenbaum A, Dimmock D, Burton BK, Stockler S, Waisbren S, Lang W, Jurecki E, Zhang C, Prasad S. Long-term developmental progression in infants and young children taking sapropterin for phenylketonuria: a two-year analysis of safety and efficacy. Genet Med. 2015 May;17(5):365-73. doi: 10.1038/gim.2014.109. Epub 2014 Sep 18. PubMed PMID: 25232857.