Sepiapterin

Sepiapterin, sold under the brand name Sephience, is a medication used for the treatment of hyperphenylalaninemia.^[2][3] Sepiapterin is a phenylalanine hydroxylase activator.^[1] It is also metabolite that is naturally synthesized in the human body.

Sepiapterin

Clinical data
Other names	Sephience
ATC code	None
Legal status
Legal status	US: ℞-only[1] EU: Rx-only[2][3]
Identifiers
IUPAC name 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-1H-pteridin-4-one
CAS Number	17094-01-8
PubChem CID	65253
IUPHAR/BPS	5276
DrugBank	DB16326
ChemSpider	58746
UNII	CJQ26KO7HP
KEGG	C00835
ChEBI	CHEBI:194527
ChEMBL	ChEMBL1255653
PDB ligand	H4B (PDBe, RCSB PDB)
Chemical and physical data
Formula	C9H11N5O3
Molar mass	237.219 g·mol−1
SMILES None
InChI InChI=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 Key:VPVOXUSPXFPWBN-VKHMYHEASA-N

The most common side effects are upper respiratory tract infection, headache, diarrhea, abdominal pain, hyperphenylalaninemia and discoloration of feces.^[2]

Biochemistry

Sepiapterin is a naturally produced metabolite that can in turn be metabolized into tetrahydrobiopterin via a salvage pathway.^[4] 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.^[5]

Medical uses

Sepiapterin is indicated for the treatment of hyperphenylalaninemia in people with phenylketonuria.^[1][2]

Side effects

The most common side effects are upper respiratory tract infection, headache, diarrhea, abdominal pain, hyperphenylalaninemia and discoloration of feces.^[2]

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.^[6]

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.^[2] The applicant for this medicinal product is PTC Therapeutics International Limited.^[2] Sepiapterin was authorized for medical use in the European Union in June 2025.^[2][3]

Sepiapterin was approved for medical use in the United States in July 2025.^[1]

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.^[7]

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.^[8]