Structure

Physi-Chem Properties

Molecular Weight:  241.12
Volume:  220.553
LogP:  -2.252
LogD:  -0.85
LogS:  -2.643
# Rotatable Bonds:  2
TPSA:  137.02
# H-Bond Aceptor:  8
# H-Bond Donor:  7
# Rings:  2
# Heavy Atoms:  8

MedChem Properties

QED Drug-Likeness Score:  0.325
Synthetic Accessibility Score:  4.779
Fsp3:  0.556
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Accepted
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -6.025
MDCK Permeability:  9.437507833354175e-05
Pgp-inhibitor:  0.0
Pgp-substrate:  0.991
Human Intestinal Absorption (HIA):  0.894
20% Bioavailability (F20%):  0.036
30% Bioavailability (F30%):  0.032

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.879
Plasma Protein Binding (PPB):  18.734024047851562%
Volume Distribution (VD):  0.592
Pgp-substrate:  71.39347839355469%

ADMET: Metabolism

CYP1A2-inhibitor:  0.005
CYP1A2-substrate:  0.113
CYP2C19-inhibitor:  0.076
CYP2C19-substrate:  0.035
CYP2C9-inhibitor:  0.015
CYP2C9-substrate:  0.011
CYP2D6-inhibitor:  0.0
CYP2D6-substrate:  0.086
CYP3A4-inhibitor:  0.004
CYP3A4-substrate:  0.083

ADMET: Excretion

Clearance (CL):  3.751
Half-life (T1/2):  0.857

ADMET: Toxicity

hERG Blockers:  0.037
Human Hepatotoxicity (H-HT):  0.97
Drug-inuced Liver Injury (DILI):  0.912
AMES Toxicity:  0.052
Rat Oral Acute Toxicity:  0.563
Maximum Recommended Daily Dose:  0.038
Skin Sensitization:  0.033
Carcinogencity:  0.672
Eye Corrosion:  0.003
Eye Irritation:  0.017
Respiratory Toxicity:  0.964

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General Info & Identifiers & Properties  
Structure MOL file  
Source Organisms  
Biological Activities  
Similar NPs/Drugs  

  Natural Product: NPC242077

Natural Product ID:  NPC242077
Common Name*:   Sapropterin
IUPAC Name:   (6R)-2-amino-6-[(1R,2S)-1,2-dihydroxypropyl]-5,6,7,8-tetrahydro-1H-pteridin-4-one
Synonyms:   Daproterin; Sapropterin
Standard InCHIKey:  FNKQXYHWGSIFBK-RPDRRWSUSA-N
Standard InCHI:  InChI=1S/C9H15N5O3/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)/t3-,4+,6-/m0/s1
SMILES:  C[C@@H]([C@@H]([C@H]1CNc2c(c(nc(=N)[nH]2)O)N1)O)O
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL1201774
PubChem CID:   44257
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000109] Pteridines and derivatives
        • [CHEMONTID:0000110] Pterins and derivatives
          • [CHEMONTID:0001651] Biopterins and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference

☑ Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  NP Quantity Composition/Concentration

Organism ID NP ID Organism Material Preparation Organism Part NP Quantity (Standard) NP Quantity (Minimum) NP Quantity (Maximum) Quantity Unit Reference

☑ Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

  Biological Activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT3569 Individual Protein Nitric-oxide synthase, brain Homo sapiens Kd = 1120.0 nM PMID[538613]
NPT3569 Individual Protein Nitric-oxide synthase, brain Homo sapiens Kcat = 8.19 /min PMID[538613]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_bilirubinemia = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_cholecystitis = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_cholelithiasis = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_cirrhosis = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_elevated liver function tests = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_hepatic failure = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_hepatic necrosis = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_hepatitis = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_hepatomegaly = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_jaundice = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_liver disease = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_liver fatty = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_liver function tests abnormal = 0.0 n.a. PMID[538614]
NPT20596 PHENOTYPE Hepatotoxicity n.a. HepSE_Combined Scores = 0.0 n.a. PMID[538614]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Hit score = 0.04545 n.a. PMID[538615]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM PMID[538616]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM PMID[538616]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 20000.0 nM PMID[538617]
NPT20555 ORGANISM SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 IC50 > 19952.62 nM PMID[538617]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

  Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

●  The left chart: Distribution of similarity level between NPC242077 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.7436 Intermediate Similarity NPC323762
0.6429 Remote Similarity NPC216278
0.6098 Remote Similarity NPC148178
0.6 Remote Similarity NPC204709
0.5981 Remote Similarity NPC62845
0.5981 Remote Similarity NPC92874
0.5981 Remote Similarity NPC166242
0.5981 Remote Similarity NPC322449
0.5981 Remote Similarity NPC189854
0.5926 Remote Similarity NPC10897
0.5926 Remote Similarity NPC325900
0.5888 Remote Similarity NPC314398
0.5888 Remote Similarity NPC239705
0.5888 Remote Similarity NPC314413
0.5765 Remote Similarity NPC41429
0.5758 Remote Similarity NPC328806
0.5732 Remote Similarity NPC193593
0.5732 Remote Similarity NPC143809
0.5732 Remote Similarity NPC76726
0.5732 Remote Similarity NPC290106
0.5699 Remote Similarity NPC202075
0.5657 Remote Similarity NPC210456
0.5657 Remote Similarity NPC190334
0.5657 Remote Similarity NPC163352
0.5657 Remote Similarity NPC62927

  Chemically structural similarity: II. Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

●  The left chart: Distribution of similarity level between NPC242077 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
1.0 High Similarity NPD9646 Approved
1.0 High Similarity NPD9644 Approved
1.0 High Similarity NPD9645 Approved
0.9125 High Similarity NPD9654 Phase 2
0.7157 Intermediate Similarity NPD284 Phase 1
0.6531 Remote Similarity NPD6424 Approved
0.6429 Remote Similarity NPD6427 Approved
0.6429 Remote Similarity NPD6423 Approved
0.6429 Remote Similarity NPD6425 Approved
0.6429 Remote Similarity NPD6426 Approved
0.6408 Remote Similarity NPD1061 Clinical (unspecified phase)
0.6392 Remote Similarity NPD6431 Approved
0.6392 Remote Similarity NPD6433 Approved
0.6392 Remote Similarity NPD6434 Clinical (unspecified phase)
0.6392 Remote Similarity NPD6432 Approved
0.6264 Remote Similarity NPD9429 Discontinued
0.6117 Remote Similarity NPD223 Clinical (unspecified phase)
0.6022 Remote Similarity NPD9558 Phase 3
0.5938 Remote Similarity NPD9640 Clinical (unspecified phase)
0.59 Remote Similarity NPD285 Discontinued
0.5795 Remote Similarity NPD2704 Phase 3
0.5795 Remote Similarity NPD2702 Phase 1
0.5743 Remote Similarity NPD251 Approved
0.5743 Remote Similarity NPD9585 Discontinued
0.573 Remote Similarity NPD5386 Phase 2
0.5699 Remote Similarity NPD8962 Discontinued
0.5682 Remote Similarity NPD3213 Discontinued
0.5663 Remote Similarity NPD1155 Discontinued
0.5657 Remote Similarity NPD9603 Phase 3
0.5657 Remote Similarity NPD9602 Phase 3
0.5657 Remote Similarity NPD241 Discontinued
0.5657 Remote Similarity NPD9604 Approved
0.5652 Remote Similarity NPD9407 Approved
0.5644 Remote Similarity NPD9565 Discontinued
0.5636 Remote Similarity NPD1385 Discontinued
0.5625 Remote Similarity NPD9573 Phase 2
0.5612 Remote Similarity NPD9401 Discovery
0.5603 Remote Similarity NPD869 Approved

  Bioactivity similarity: Similar Natural Products in NPASS

Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.

Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity
B: biological targets similarity
C: networks similarity
D: cell-based bioactivity similarity
E: similarity based on clinical data