{{Short description|Medication}} {{Use dmy dates|date=December 2024}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | image = Sepiapterin.png | image_class = skin-invert-image | width = | alt = | caption =
<!-- Clinical data --> | pronounce = | tradename = Sephience | Drugs.com = {{drugs.com|monograph|sepiapterin}} | MedlinePlus = a625095 | DailyMedID = Sepiapterin | pregnancy_AU = | pregnancy_AU_comment = | pregnancy_category= | routes_of_administration = By mouth | class = | ATC_prefix = A16 | ATC_suffix = AX28 | ATC_supplemental =
<!-- Legal status --> | legal_AU = S4 | legal_AU_comment = <ref>{{cite web | title=Sephience (Ptc Therapeutics Australia Pty Limited) | website=Therapeutic Goods Administration (TGA) | date=24 September 2025 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/sephience-ptc-therapeutics-australia-pty-limited | access-date=20 October 2025}}</ref> | legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C5, D1, D2, E, F1, F2, F3, F4 --> | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref>{{cite web | title=Sephience Product information | website=Health Canada | date=7 October 2025 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=106475 | access-date=8 November 2025}}</ref><ref>{{cite web | title=Summary Basis of Decision for Sephience | website=Drug and Health Products Portal | date=18 December 2025 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1766001787668 | access-date=17 February 2026}}</ref> | legal_DE = <!-- Anlage I, II, III or Unscheduled --> | legal_DE_comment = | legal_NZ = <!-- Class A, B, C --> | legal_NZ_comment = | legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C --> | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Sephience FDA label">{{cite web | title=Sephience- sepiapterin powder | website=DailyMed | date=28 July 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32ac719c-49f0-4105-9c46-18c19583a5c2 | access-date=20 October 2025}}</ref><ref>{{cite web | title=Sephience- sepiapterin powder | website=DailyMed | date=2 October 2025 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9fabfee2-9488-4d03-b203-8fa50f9a7f55 | access-date=20 October 2025}}</ref> | legal_EU = Rx-only | legal_EU_comment = <ref name="Sephience EPAR" /><ref name="Sephience PI" /> | legal_UN = <!-- N I, II, III, IV / P I, II, III, IV --> | legal_UN_comment = | legal_status = <!-- For countries not listed above -->
<!-- Pharmacokinetic data --> | bioavailability = | protein_bound = | metabolism = | metabolites = | onset = | elimination_half-life = | duration_of_action= | excretion =
<!-- Identifiers --> | CAS_number = 17094-01-8 | PubChem = 65253 | IUPHAR_ligand = 5276 | DrugBank = DB16326 | ChemSpiderID = 58746 | UNII = CJQ26KO7HP | KEGG = C00835 | ChEBI = 194527 | ChEMBL = 1255653 | NIAID_ChemDB = | PDB_ligand = H4B | synonyms = Sephience
<!-- Chemical and physical data --> | IUPAC_name = <nowiki>2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one</nowiki> | C=9 | H=11 | N=5 | O=3 | SMILES = None | StdInChI = InChI=1S/C9H11N5O3/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7/h3,15H,2H2,1H3,(H4,10,11,13,14,17)/t3-/m0/s1 | StdInChI_comment = | StdInChIKey = VPVOXUSPXFPWBN-VKHMYHEASA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}
'''Sepiapterin''', sold under the brand name '''Sephience''', is a medication used for the treatment of hyperphenylalaninemia.<ref name="Sephience EPAR" /><ref name="Sephience PI" /> Sepiapterin is a phenylalanine hydroxylase activator.<ref name="Sephience FDA label" /> It is also metabolite that is naturally synthesized in the human body.
The most common side effects are upper respiratory tract infection, headache, diarrhea, abdominal pain, hyperphenylalaninemia and discoloration of feces.<ref name="Sephience EPAR" />
== Biochemistry == Sepiapterin is a naturally produced metabolite that can in turn be metabolized into tetrahydrobiopterin via a salvage pathway.<ref name="Hasegawa_2005">{{cite journal | vauthors = Hasegawa H, Sawabe K, Nakanishi N, Wakasugi OK | title = Delivery of exogenous tetrahydrobiopterin (BH4) to cells of target organs: role of salvage pathway and uptake of its precursor in effective elevation of tissue BH4 | journal = Molecular Genetics and Metabolism | volume = 86 Suppl 1 | issue = | pages = S2–10 | date = December 2005 | pmid = 16256391 | doi = 10.1016/j.ymgme.2005.09.002 }}</ref> Tetrahydrobiopterin is an essential cofactor in humans for breakdown of phenylalanine and a catalyst of the metabolism of phenylalanine, tyrosine, and tryptophan to precursors of the neurotransmitters dopamine and serotonin.<ref name="Werner_2011">{{cite journal | vauthors = Werner ER, Blau N, Thöny B | title = Tetrahydrobiopterin: biochemistry and pathophysiology | journal = The Biochemical Journal | volume = 438 | issue = 3 | pages = 397–414 | date = September 2011 | pmid = 21867484 | doi = 10.1042/BJ20110293 }}</ref>
== Medical uses == Sepiapterin is indicated for the treatment of hyperphenylalaninemia in people with phenylketonuria.<ref name="Sephience FDA label" /><ref name="Sephience EPAR" />
== Side effects == The most common side effects are upper respiratory tract infection, headache, diarrhea, abdominal pain, hyperphenylalaninemia and discoloration of feces.<ref name="Sephience EPAR" />
== Mechanism of action == Sepiapterin is a metabolite that is naturally synthesized in the human body. Synthetic sepiapterin also functions as a prodrug that serves as a precursor to tetrahydrobiopterin (BH4). The therapeutic effect of sepiapterin results from its conversion to BH4, which functions as a cofactor for phenylalanine hydroxylase (PAH). This enzymatic activity enables patients with phenylketonuria (PKU) to better metabolize phenylalanine, thereby reducing its neurotoxic concentration in the blood.<ref>{{cite web | title = Sepiapterin | url = https://go.drugbank.com/drugs/DB16326 | work = DrugBank }}</ref>
== Society and culture == === Legal status === In April 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Sephience, intended for the treatment of hyperphenylalaninemia in adults and children with phenylketonuria.<ref name="Sephience EPAR" /> The applicant for this medicinal product is PTC Therapeutics International Limited.<ref name="Sephience EPAR">{{cite web | title = Sephience EPAR | date = 25 April 2025 | publisher = European Medicines Agency (EMA) | url = https://www.ema.europa.eu/en/medicines/human/EPAR/sephience | access-date = 2 May 2025 }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Sepiapterin was authorized for medical use in the European Union in June 2025.<ref name="Sephience EPAR" /><ref name="Sephience PI">{{cite web | title = Sephience Product information | date = 25 June 2025 | website = Union Register of medicinal products | url = https://ec.europa.eu/health/documents/community-register/html/h1939.htm | access-date = 27 June 2025 }}</ref>
Sepiapterin was approved for medical use in the United States in July 2025.<ref name="Sephience FDA label" />
== Research == Deficiency of tetrahydrobiopterin can cause toxic buildup of phenylalanine (phenylketonuria) as well as deficiencies of dopamine, norepinephrine, and epinephrine, leading to dystonia and other neurological illnesses. This has led to clinical study of sepiapterin in humans to treat tetrahydrobiopterin deficiency.<ref name="Smith_2019">{{cite journal | vauthors = Smith N, Longo N, Levert K, Hyland K, Blau N | title = Phase I clinical evaluation of CNSA-001 (sepiapterin), a novel pharmacological treatment for phenylketonuria and tetrahydrobiopterin deficiencies, in healthy volunteers | journal = Molecular Genetics and Metabolism | volume = 126 | issue = 4 | pages = 406–412 | date = April 2019 | pmid = 30922814 | doi = 10.1016/j.ymgme.2019.02.001 | s2cid = 85564348 }}</ref>
Since atherosclerosis and other circulatory diseases associated with diabetes are also associated with tetrahydrobiopterin deficiency, animal studies of the value of sepiaterin in these vascular diseases have been done. These studies show that relaxation of the blood vessels studied was impaired after animals were given sepiapterin, even though their levels of tetrahydrobiopterin were replenished.<ref name="VasquezVivar_2002">{{cite journal | vauthors = Vásquez-Vivar J, Duquaine D, Whitsett J, Kalyanaraman B, Rajagopalan S | title = Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 22 | issue = 10 | pages = 1655–1661 | date = October 2002 | pmid = 12377745 | doi = 10.1161/01.ATV.0000029122.79665.D9 | doi-access = free }}</ref>
== References == {{Reflist}}
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