Natural Product: NPC231013

Natural Product IDNPC231013
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2,3-Dimethoxyxanthen-9-One
IUPAC Name 2,3-dimethoxyxanthen-9-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1434162
PubChem CID 253955
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000123] Benzopyrans
        • [CHEMONTID:0003410] 1-benzopyrans
          • [CHEMONTID:0002817] Dibenzopyrans
            • [CHEMONTID:0000200] Xanthenes
              • [CHEMONTID:0000204] Xanthones

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 FWCWUPRCWDSQEN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H12O4/c1-17-13-7-10-12(8-14(13)18-2)19-11-6-4-3-5-9(11)15(10)16/h3-8H,1-2H3
SMILES COc1cc2c(cc1OC)oc1c(c2=O)cccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   256.07 Volume:   259.033
?
Van der Waals volume.
Dense:   0.989 LogP:   2.193
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.352
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.757
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   17.0
TPSA:   48.67
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.661 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.814 Fsp3:   0.133
MCE-18:   16.0
?
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:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.098 Fluc inhibitor:   0.961
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.833
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.469
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.564 Promiscuous compounds:   0.791

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.673 MDCK Permeability:   -4.618
Pgp-inhibitor:   0.957 Pgp-substrate:   0.091
PAMPA:   0.026
?
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):   0.085
20% Bioavailability (F20%):   0.108 30% Bioavailability (F30%):   0.255
50% Bioavailability (F50%):   0.759

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.017 MRP1:   0.786
Plasma Protein Binding (PPB):   93.661% Volume Distribution (VD):   0.045
Fu: 6.206%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.974
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.992
BSEP inhibitor:   0.996

ADMET: Metabolism

CYP1A2-inhibitor:   0.996 CYP1A2-substrate:   0.542
CYP2C19-inhibitor:   0.745 CYP2C19-substrate:   0.223
CYP2C9-inhibitor:   0.778 CYP2C9-substrate:   0.022
CYP2D6-inhibitor:   0.896 CYP2D6-substrate:   0.615
CYP3A4-inhibitor:   0.939 CYP3A4-substrate:   0.756
CYP2B6-substrate:   0.407 CYP2C8-inhibitor:   0.29
HLM stability:   0.459
?
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):  3.998 Half-life (T1/2):  2.283

ADMET: Toxicity

hERG Blockers:  0.126 hERG Blockers (10um):  0.496
Human Hepatotoxicity (H-HT):  0.483 Drug-induced Liver Injury (DILI):  0.793
AMES Toxicity:  0.615 Rat Oral Acute Toxicity:  0.501
Maximum Recommended Daily Dose:  0.5 Skin Sensitization:  0.427
Carcinogencity:  0.83 Eye Corrosion:  0.753
Eye Irritation:  0.989 Respiratory Toxicity:  0.701
Drug-induced Neurotoxicity:  0.336 Ototoxicity:  0.124
Hematotoxicity:  0.32 Drug-induced Nephrotoxicity:  0.136
Genotoxicity:  0.449 RPMI-8226 Immunitoxicity:  0.059
A549 Cytotoxicity:  0.095 Hek293 Cytotoxicity:  0.284
BCF:   1.521
?
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:   3.832
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.496
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.237
?
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
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota roots n.a. n.a. PMID[16989524]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. rhizome n.a. PMID[22863942]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota aerial parts n.a. n.a. PMID[24042007]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. PMID[38838926]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO27260 Polygala tenuifolia Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO27260 Polygala tenuifolia Species Polygalaceae 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
NPT199 Individual protein DNA polymerase kappa Homo sapiens Potency n.a. 89125.1 nM PubChem BioAssay data set
NPT156 Individual protein Sphingomyelin phosphodiesterase Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 10000.0 nM PubChem BioAssay data set
NPT1853 Individual protein Putative uncharacterized protein Trypanosoma brucei brucei (strain 927/4 GUTat10.1) Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT101 Individual protein Glucagon-like peptide 1 receptor Homo sapiens Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT160 Individual protein TAR DNA-binding protein 43 Homo sapiens Potency n.a. 15848.9 nM PubChem BioAssay data set
NPT803 Individual protein Flap endonuclease 1 Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT54 Individual protein Nonstructural protein 1 Influenza A virus Potency = 3548.1 nM PubChem BioAssay data set
NPT538 Individual protein Niemann-Pick C1 protein Homo sapiens Potency = 5623.4 nM PubChem BioAssay data set
NPT61 Individual protein Beta-glucocerebrosidase Homo sapiens Potency n.a. 12589.3 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 39810.7 nM PubChem BioAssay data set
NPT484 Individual protein Luciferin 4-monooxygenase Photinus pyralis Potency n.a. 19011.5 nM PubChem BioAssay data set
NPT7 Individual protein Thioredoxin reductase 1, cytoplasmic Rattus norvegicus Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 28183.8 nM PubChem BioAssay data set
NPT920 Individual protein Alpha-synuclein Homo sapiens Potency n.a. 35481.3 nM PubChem BioAssay data set
NPT741 Individual protein Tyrosinase Homo sapiens IC50 = 8290.0 nM PMID[33242700]
NPT741 Individual protein Tyrosinase Homo sapiens Inhibition = 90.5 % PMID[33242700]
NPT442 Individual protein Ferritin light chain Equus caballus Potency = 11220.2 nM PubChem BioAssay data set
NPT197 Protein-protein interaction Menin/Histone-lysine N-methyltransferase MLL Homo sapiens Potency = 39810.7 nM PubChem BioAssay data set
NPT56 Individual protein Beta-lactamase AmpC Escherichia coli K-12 Potency = 35481.3 nM PubChem BioAssay data set
NPT443 Individual protein Histone acetyltransferase GCN5 Homo sapiens Potency n.a. 794.3 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 20587.8 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 2908.1 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT65 Cell line HepG2 Homo sapiens Potency n.a. 6309.6 nM PubChem BioAssay data set
NPT520 Cell line 3T3-L1 Mus musculus Activity = 0.0 % PMID[29626799]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 3696.4 nM PubChem BioAssay data set
NPT20 Organism Candida albicans Candida albicans MIC = 31.3 ug.mL-1 PMID[22014830]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 62.5 ug.mL-1 PMID[22014830]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC = 31.3 ug.mL-1 PMID[22014830]
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PubChem BioAssay data set
NPT314 Organism Bacillus cereus Bacillus cereus MIC = 46.9 ug.mL-1 PMID[22014830]
NPT1140 Organism Escherichia coli ATCC 8739 Escherichia coli ATCC 8739 MIC = 125.0 ug.mL-1 PMID[22014830]
NPT1121 Organism Moraxella catarrhalis Moraxella catarrhalis MIC = 125.0 ug.mL-1 PMID[22014830]
NPT2 Others Unspecified n.a. Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 446.7 nM PubChem BioAssay data set

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT617 Organism Danio rerio Danio rerio EC50 = 280.0 nM PMID[29626799]
NPT617 Organism Danio rerio Danio rerio Activity = 0.0 % PMID[29626799]
NPT617 Organism Danio rerio Danio rerio FC = 2.0 n.a. PMID[29626799]





 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 NPC231013 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
0.7045 Intermediate Similarity NPC605893
0.6458 Remote Similarity NPC292214
0.6316 Remote Similarity NPC475269
0.6316 Remote Similarity NPC35744
0.62 Remote Similarity NPC88645
0.6122 Remote Similarity NPC17055
0.6042 Remote Similarity NPC608827
0.5849 Remote Similarity NPC244371
0.549 Remote Similarity NPC200221
0.549 Remote Similarity NPC610896
0.5435 Remote Similarity NPC29056
0.5385 Remote Similarity NPC608745
0.5283 Remote Similarity NPC179183
0.5283 Remote Similarity NPC294502
0.5283 Remote Similarity NPC271779

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC231013 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