Sepiapterin

Summary

Sepiapterin (CHEMBL1255653) is a phase-3 clinical-stage small molecule targeting PAH; indicated across 2 conditions including phenylketonuria and gastroparesis.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (PAH)
• Indications: 2 conditions
• Clinical trials: 5
• Chemistry: 237.22 Da · C9H11N5O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1255653
Name	Sepiapterin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	135398579
Molecular formula	C9H11N5O3
Molecular weight	237.22
InChIKey	VPVOXUSPXFPWBN-VKHMYHEASA-N

SMILES: C[C@@H](C(=O)C1=NC2=C(NC1)N=C(NC2=O)N)O

IUPAC name: 2-amino-6-[(2S)-2-hydroxypropanoyl]-7,8-dihydro-3H-pteridin-4-one

Also known as: CNSA-001, L-sepiapterin, PTC-923, PTC923, Sepiapterin, Sepiapterina, Sepiapterine, SID11111762, SID50107031, SID90341319, SID56462995, SID50107032

Patent coverage: 208 distinct patent families (676 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 652 (96%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PAH	L-Phenylalanine hydroxylase	Activation		0.2%	P00439

Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Microtubule-associated protein tau, Lysine-specific demethylase 4E, Prelamin-A/C, RecQ-like DNA helicase BLM, Ferritin light chain, Menin/Histone-lysine N-methyltransferase MLL, Muscarinic acetylcholine receptor M1, Cytochrome P450 3A4, Caspase-7, Guanine nucleotide-binding protein G(i) subunit alpha-1/Regulator of G-protein signaling 12.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
BLM	8.66	Potency	2.2	nM	CHEMBL_ACT_4749980
BLM	8.66	Potency	2.2	nM	CHEMBL_ACT_4937851
CYP3A4	6.5	Potency	316.2	nM	CHEMBL_ACT_4977616
CYP3A4	6.5	Potency	316.2	nM	CHEMBL_ACT_5046609
CYP3A4	6.5	AC50	316.2	nM	CHEMBL_ACT_6061764
LMNA	5.2	Potency	6310	nM	CHEMBL_ACT_3660292
P08482	5.05	Potency	8912	nM	CHEMBL_ACT_4799554
HIF1A	5	Potency	10000	nM	CHEMBL_ACT_4129664
HIF1A	5	Potency	10000	nM	CHEMBL_ACT_4518700

Target pathways

Aggregated over 1 target gene(s): PAH.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Phenylketonuria	1	PAH
Phenylalanine metabolism	1	PAH

Dominant GO biological processes

GO term	Targets
L-phenylalanine catabolic process	1
L-tyrosine biosynthetic process	1
amino acid biosynthetic process	1
catecholamine biosynthetic process	1
aromatic amino acid metabolic process	1
obsolete L-tyrosine biosynthetic process, by oxidation of phenylalanine	1

Indications & clinical

Indications

2 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
phenylketonuria	3	MONDO:0009861	MONDO:0009861
gastroparesis	2	MONDO:0006769	EFO:1000948

Clinical trials

Total trials: 5.

Phase distribution

Phase	Trials
PHASE3	3
PHASE1/PHASE2	1
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05166161	PHASE3	ACTIVE_NOT_RECRUITING	A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
NCT06302348	PHASE3	RECRUITING	A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
NCT05099640	PHASE3	COMPLETED	A Study of PTC923 in Participants With Phenylketonuria
NCT03519711	PHASE1/PHASE2	COMPLETED	A Study of PTC923 (CNSA-001) in Primary Tetrahydrobiopterin (BH4) Deficient Participants With Hyperphenylalaninemia
NCT03712124	PHASE2	COMPLETED	A Study of CNSA-001 in Women With Diabetic Gastroparesis

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).