Natural Product: NPC479110

Natural Product IDNPC479110
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 PARYRHHOYYLEBN-LOKQZNEXSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 127025174
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0002699] Benzodioxanes
        • [CHEMONTID:0002704] Phenylbenzodioxanes
          • [CHEMONTID:0002707] Phenylbenzo-1,4-dioxanes

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

  Chemical Representations

Standard InCHIKey PARYRHHOYYLEBN-LOKQZNEXSA-N
Standard InCHI InChI=1S/C20H20O6/c1-23-15-8-6-14(11-17(15)24-2)20-19(12-22)25-18-10-13(4-3-9-21)5-7-16(18)26-20/h3-11,19-20,22H,12H2,1-2H3/b4-3+/t19-,20-/m0/s1
SMILES COc1ccc(cc1OC)[C@H]1[C@H](CO)Oc2cc(/C=C/C=O)ccc2O1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.13 Volume:   360.456
?
Van der Waals volume.
Dense:   0.988 LogP:   2.661
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.694
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.082
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   19.0
TPSA:   74.22
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.634 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.237 Fsp3:   0.25
MCE-18:   53.72
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.843 Fluc inhibitor:   0.949
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.172
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.486
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.373 Promiscuous compounds:   0.286

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.368 MDCK Permeability:   -5.086
Pgp-inhibitor:   1.0 Pgp-substrate:   0.01
PAMPA:   0.008
?
The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).
 Human Intestinal Absorption (HIA):   0.002
20% Bioavailability (F20%):   0.062 30% Bioavailability (F30%):   0.502
50% Bioavailability (F50%):   0.315

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.33 MRP1:   0.032
Plasma Protein Binding (PPB):   92.207% Volume Distribution (VD):   -0.116
Fu: 6.786%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.964
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   0.596 CYP1A2-substrate:   0.07
CYP2C19-inhibitor:   0.233 CYP2C19-substrate:   0.004
CYP2C9-inhibitor:   0.003 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.004 CYP2D6-substrate:   0.099
CYP3A4-inhibitor:   0.904 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.986
HLM stability:   0.0
?
Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):  8.101 Half-life (T1/2):  1.208

ADMET: Toxicity

hERG Blockers:  0.19 hERG Blockers (10um):  0.296
Human Hepatotoxicity (H-HT):  0.759 Drug-induced Liver Injury (DILI):  0.701
AMES Toxicity:  0.813 Rat Oral Acute Toxicity:  0.395
Maximum Recommended Daily Dose:  0.135 Skin Sensitization:  0.942
Carcinogencity:  0.589 Eye Corrosion:  0.064
Eye Irritation:  0.919 Respiratory Toxicity:  0.372
Drug-induced Neurotoxicity:  0.819 Ototoxicity:  0.457
Hematotoxicity:  0.375 Drug-induced Nephrotoxicity:  0.696
Genotoxicity:  0.775 RPMI-8226 Immunitoxicity:  0.106
A549 Cytotoxicity:  0.133 Hek293 Cytotoxicity:  0.169
BCF:   1.086
?
Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].
 IGC50:   3.687
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.397
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.796
?
96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

  Species Source

Organism ID Organism Name Taxonomy Level Family SuperKingdom Isolation Part Collection Location Collection Time Reference
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota roots n.a. n.a. PMID[18177012]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota Seeds n.a. n.a. PMID[26595875]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota Fruit n.a. n.a. Database[FooDB]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota Shoot n.a. n.a. Database[FooDB]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. Database[FooDB]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO17551 Phytolacca americana Species Phytolaccaceae Eukaryota n.a. n.a. n.a. Database[UNPD]

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 Organism Name 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

Molecular-level activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 4000.0 nM PMID[26595875]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference





 Experimental ADME

Experiment Model Experiment Tissue ADME Type ADME Relation ADME Value ADME Unit Reference





 Experimental Toxicity

Quantitative toxicity

Experiment Model Experiment Organism Toxicity Type Toxicity Relation Toxicity Value Toxicity Unit Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption
Hepatotoxicity Carcinogenicity Mutagenicity Cardiotoxicity Respiratory Toxicity Eye Irritation Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]


  Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

●  The left chart: Distribution of similarity level between NPC479110 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.5 or Top200).

Similarity Score Similarity Level Natural Product ID
0.8 Intermediate Similarity NPC479108
0.7455 Intermediate Similarity NPC214729
0.7193 Intermediate Similarity NPC83375
0.6667 Remote Similarity NPC479112
0.6667 Remote Similarity NPC479111
0.661 Remote Similarity NPC488544
0.6167 Remote Similarity NPC30083
0.6032 Remote Similarity NPC224876
0.5968 Remote Similarity NPC278469
0.5909 Remote Similarity NPC126206
0.5873 Remote Similarity NPC249791
0.5833 Remote Similarity NPC179309
0.5806 Remote Similarity NPC193722
0.5667 Remote Similarity NPC72529
0.5625 Remote Similarity NPC471664
0.5625 Remote Similarity NPC471665
0.5538 Remote Similarity NPC479113
0.5152 Remote Similarity NPC476387
0.5152 Remote Similarity NPC237594
0.5152 Remote Similarity NPC119060
0.5077 Remote Similarity NPC488546

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC479110 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
NPD

Bioactivity similarity

  Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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