Sapropterin
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Also known as 6r-bh4DapropterinR-thbpSapropterinaSapropterineTetrahydrobiopterinDAPROPTERIN DIHYDROCHLORIDE
Summary
Sapropterin (CHEMBL1201774) is an approved small-molecule diagnostic agent (ATC A16AX07) targeting PAH; indicated across 12 conditions including autism and chronic obstructive pulmonary disease.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: A16AX07
- Targets: 1 (PAH)
- Indications: 12 conditions
- Clinical trials: 26
- Chemistry: 241.25 Da · C9H15N5O3
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1201774 |
| Name | Sapropterin |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 135398654 |
| ChEBI | CHEBI:59560 |
| ATC | A16AX07 |
| Molecular formula | C9H15N5O3 |
| Molecular weight | 241.25 |
| InChIKey | FNKQXYHWGSIFBK-RPDRRWSUSA-N |
SMILES: C[C@@H]([C@@H]([C@H]1CNC2=C(N1)C(=O)NC(=N2)N)O)O
IUPAC name: (6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-3H-pteridin-4-one
ChEBI definition: A tetrahydropterin that is 2-amino-5,6,7,8-tetrahydropteridin-4(3H)-one in which a hydrogen at position 6 is substituted by a 1,2-dihydroxypropyl group (6R,1’R,2’S-enantiomer).
Pharmacological roles (ChEBI): coenzyme, diagnostic agent, cofactor.
Other ChEBI roles (chemical / environmental): human metabolite.
Also known as: 6r-bh4, Dapropterin, R-thbp, Sapropterin, Sapropterina, Sapropterine, Tetrahydrobiopterin, tetrahydrobiopterin, SAPROPTERIN, sapropterin, DAPROPTERIN DIHYDROCHLORIDE
Parent form; salt/anhydrous children: CHEMBL1201775, CHEMBL1515624
Patent coverage: 974 distinct patent families (2,511 SureChEMBL compound mentions), from 2 matched compound structure(s). 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 | 5.4 | 0.2% | P00439 |
Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Nitric oxide synthase 1.
Bioactivity
ChEMBL activities: 1 potent at pChembl ≥ 5 of 1 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| NOS1 | 5.95 | Kd | 1120 | nM | CHEMBL_ACT_2109345 |
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
12 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 |
|---|---|---|---|
| autism | 2 | MONDO:0005260 | EFO:0003758 |
| chronic obstructive pulmonary disease | 2 | MONDO:0005002 | EFO:0000341 |
| portal hypertension | 2 | MONDO:0005080 | EFO:0000666 |
| cirrhosis of liver | 2 | MONDO:0005155 | EFO:0001422 |
| Alzheimer disease | 2 | MONDO:0004975 | MONDO:0004975 |
| phenylketonuria | 2 | MONDO:0009861 | MONDO:0009861 |
| Lesch-Nyhan syndrome | 2 | MONDO:0010298 | MONDO:0010298 |
| enteritis | 2 | MONDO:0043579 | MONDO:0043579 |
| chronic kidney disease | 2 | MONDO:0005300 | MONDO:0024327 |
| radiodermatitis | 1 | MONDO:0043771 | MONDO:0043771 |
| hypertensive disorder | 0 | MONDO:0005044 | EFO:0000537 |
| heart failure | 0 | MONDO:0005252 | EFO:0003144 |
Clinical trials
Total trials: 26.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE2 | 9 |
| Not specified | 6 |
| PHASE1 | 4 |
| PHASE2/PHASE3 | 3 |
| EARLY_PHASE1 | 2 |
| PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00104247 | PHASE3 | COMPLETED | Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels |
| NCT00432822 | PHASE2/PHASE3 | TERMINATED | Long-Term Tetrahydrobiopterin Treatment in PKU Patients of 0-18 Years - Study on Phenylalanine Tolerance and Safety |
| NCT00935753 | PHASE2/PHASE3 | WITHDRAWN | Trial of Kuvan in Lesch-Nyhan Disease |
| NCT01456286 | PHASE2/PHASE3 | COMPLETED | Randomized Controlled Trial to Assess the Effects of Sapropterin on Hepatic and Systemic Hemodynamics in Patients With Liver Cirrhosis and Portal Hypertension |
| NCT02947750 | PHASE2 | RECRUITING | Neurovascular Transduction During Exercise in Chronic Kidney Disease |
| NCT00423280 | PHASE2 | UNKNOWN | Effect of 6R-BH4 Treatment in Coronary Artery Disease (OXBIO Study) |
| NCT00802893 | PHASE2 | TERMINATED | Oral 6R-BH4 for the Treatment of Isolated Systolic Hypertension and Endothelial Dysfunction |
| NCT00850070 | PHASE2 | COMPLETED | Sapropterin as a Treatment for Autistic Disorder |
| NCT01356966 | PHASE2 | COMPLETED | Exercise Intolerance in Renal Failure |
| NCT01425528 | PHASE1/PHASE2 | COMPLETED | Study of Kuvan Treatment in Adults With GTPCH Deficiency |
| NCT01439555 | PHASE2 | COMPLETED | Endothelial Facilitation in Alzheimer’s Disease |
| NCT01977820 | PHASE2 | TERMINATED | Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria |
| NCT02774226 | PHASE2 | COMPLETED | Long Term Nitric Oxide Bioavailability on Vascular Health in Chronic Obstructive Pulmonary Disease |
| NCT05138887 | PHASE2 | UNKNOWN | A Study for Assessing the Efficacy and Safety of BH4 in Radiation Enteritis |
| NCT04800692 | PHASE1 | ACTIVE_NOT_RECRUITING | The Effects of ATLAS Therapy on Nitric Oxide Bioavailability in Patients With Intermittent Claudication |
| NCT00244218 | PHASE1 | TERMINATED | Response to Phenylketonuria to Tetrahydrobiopterin (BH4) |
| NCT04014712 | PHASE1 | WITHDRAWN | O2 Transport and Utilization in Health and Lung Disease |
| NCT05114226 | PHASE1 | UNKNOWN | A Study for Assessing the Efficacy and Safety of Tetrahydrobiopterin in Radiation-Induced Skin Injury |
| NCT00208780 | EARLY_PHASE1 | COMPLETED | Effects of Tetrahydrobiopterin on Blood Pressure |
| NCT03136029 | EARLY_PHASE1 | COMPLETED | Exercise and NO in HFrEF |
| NCT00730080 | Not specified | COMPLETED | Sapropterin in Individuals With Phenylketonuria |
| NCT00964236 | Not specified | COMPLETED | The Effects of Kuvan on Functional Brain Connectivity in Individuals With Phenylketonuria (PKU) |
| NCT00986973 | Not specified | COMPLETED | Fluorodeoxyglucose Positron Emission Tomography (FDG PET) Findings in Patients With Phenylketonuria Before and After KUVAN Therapy |
| NCT01398943 | Not specified | COMPLETED | Nitric Oxide Bioavailability in Chronic Obstructive Pulmonary Disease (COPD) |
| NCT01541397 | Not specified | TERMINATED | Bone Mineral Density in Adults With Hyperphenylalaninemia on Kuvan Therapy |
| NCT03820804 | Not specified | COMPLETED | Nutritional Status in Phenylketonuria |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).
Related Atlas pages
- Genes: PAH