Natural Product: NPC199100

Natural Product IDNPC199100
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Bellidifolin
IUPAC Name 1,5,8-trihydroxy-3-methoxyxanthen-9-one
Synonyms Bellidifolin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL185776
PubChem CID 5281623
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 JDIORNFCMMYMLF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H10O6/c1-19-6-4-9(17)11-10(5-6)20-14-8(16)3-2-7(15)12(14)13(11)18/h2-5,15-17H,1H3
SMILES COc1cc(O)c2c(c1)oc1c(c2=O)c(O)ccc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.05 Volume:   259.317
?
Van der Waals volume.
Dense:   1.057 LogP:   2.006
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.189
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.907
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   17.0
TPSA:   100.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   3.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.464 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.493 Fsp3:   0.071
MCE-18:   18.0
?
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:   0.613 Fluc inhibitor:   0.502
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.687
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.373
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.502 Promiscuous compounds:   0.862

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.079 MDCK Permeability:   -4.787
Pgp-inhibitor:   0.431 Pgp-substrate:   0.368
PAMPA:   0.226
?
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):   0.228
20% Bioavailability (F20%):   0.148 30% Bioavailability (F30%):   0.683
50% Bioavailability (F50%):   0.939

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.007 MRP1:   0.624
Plasma Protein Binding (PPB):   95.39% Volume Distribution (VD):   -0.231
Fu: 4.37%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.915
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.901
BSEP inhibitor:   0.814

ADMET: Metabolism

CYP1A2-inhibitor:   0.884 CYP1A2-substrate:   0.601
CYP2C19-inhibitor:   0.166 CYP2C19-substrate:   0.166
CYP2C9-inhibitor:   0.949 CYP2C9-substrate:   0.022
CYP2D6-inhibitor:   0.722 CYP2D6-substrate:   0.851
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.059
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.918
HLM stability:   0.899
?
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):  7.365 Half-life (T1/2):  1.1

ADMET: Toxicity

hERG Blockers:  0.044 hERG Blockers (10um):  0.373
Human Hepatotoxicity (H-HT):  0.405 Drug-induced Liver Injury (DILI):  0.97
AMES Toxicity:  0.755 Rat Oral Acute Toxicity:  0.62
Maximum Recommended Daily Dose:  0.659 Skin Sensitization:  0.408
Carcinogencity:  0.804 Eye Corrosion:  0.265
Eye Irritation:  0.993 Respiratory Toxicity:  0.801
Drug-induced Neurotoxicity:  0.012 Ototoxicity:  0.066
Hematotoxicity:  0.151 Drug-induced Nephrotoxicity:  0.034
Genotoxicity:  0.92 RPMI-8226 Immunitoxicity:  0.056
A549 Cytotoxicity:  0.182 Hek293 Cytotoxicity:  0.346
BCF:   1.13
?
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:   3.649
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.416
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.851
?
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
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1007/BF02675902]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4039(00)72792-4]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4039(00)95355-3]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1055/s-2008-1074888]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1248/cpb.30.4088]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. DOI[10.1248/cpb.30.4088]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[10353265]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[11858759]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[16499318]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[16562838]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[17524651]
NPO32688 gentianella amarella ssp. acuta Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[18336006]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[18406151]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[20627740]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. PMID[20718449]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[26996316]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[4712626]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[5583807]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[Article]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28502 Rhabdastrella globostellata Species Ancorinidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13329 Tephrosia polystachyoides Species Geometridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7994 Derris laxiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15801 Hunteria umbellata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO28996 Caloglossa leprieurii Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO32688 gentianella amarella ssp. acuta Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28996 Caloglossa leprieurii Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8844 Stillingia sylvatica Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8844 Stillingia sylvatica Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO28996 Caloglossa leprieurii Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO30223 Swertia chirata Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO31193 Gentiana campestris Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO7994 Derris laxiflora Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16479 Tigridia pavonia Species Iridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15801 Hunteria umbellata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14940 Cedronella cana Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22057 Gentiana kochiana Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13329 Tephrosia polystachyoides Species Geometridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO29129 Rhodiola heterodonta Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28996 Caloglossa leprieurii Species Delesseriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10647 Gentiana lactea Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23442 Cachonina hallii Species Heterocapsaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8844 Stillingia sylvatica Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28011 Swertia japonica Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14381 Swertia pseudochinensis Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28502 Rhabdastrella globostellata Species Ancorinidae 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
NPT261 Individual protein Monoamine oxidase A Homo sapiens IC50 = 660.0 nM PMID[15482934]
NPT204 Individual protein Acetylcholinesterase Homo sapiens Inhibition = 21.9 % PMID[18336006]
NPT261 Individual protein Monoamine oxidase A Homo sapiens Inhibition = 98.9 % PMID[18336006]
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 7943.3 nM PubChem BioAssay data set
NPT582 Individual protein Monoamine oxidase B Homo sapiens Inhibition = 65.2 % PMID[18336006]
NPT803 Individual protein Flap endonuclease 1 Homo sapiens Potency n.a. 25118.9 nM PubChem BioAssay data set
NPT8 Individual protein DNA polymerase iota Homo sapiens Potency n.a. 56234.1 nM PubChem BioAssay data set
NPT755 Individual protein Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 Homo sapiens Potency n.a. 50118.7 nM PubChem BioAssay data set
NPT532 Individual protein Lysine-specific demethylase 4A Homo sapiens Potency n.a. 63095.7 nM PubChem BioAssay data set
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 3013.1 nM PubChem BioAssay data set
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 8492.1 nM PubChem BioAssay data set
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 11577.4 nM PubChem BioAssay data set
NPT62 Individual protein 6-phospho-1-fructokinase Trypanosoma brucei Potency n.a. 2685.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT76 Cell line C6 Rattus norvegicus IC50 > 100000.0 nM PMID[18406151]
NPT380 Cell line U-251 Homo sapiens IC50 > 100000.0 nM PMID[18406151]
NPT2 Others Unspecified n.a. IC50 > 50000.0 nM PMID[18406151]
NPT2 Others Unspecified n.a. Potency n.a. 6513.1 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 31622.8 nM PubChem BioAssay data set

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 NPC199100 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
0.74 Intermediate Similarity NPC29231
0.6346 Remote Similarity NPC62042
0.6226 Remote Similarity NPC188167
0.6154 Remote Similarity NPC180234
0.6 Remote Similarity NPC486841
0.5926 Remote Similarity NPC120537
0.5849 Remote Similarity NPC310340
0.58 Remote Similarity NPC61620
0.5741 Remote Similarity NPC609936
0.5636 Remote Similarity NPC117579
0.5636 Remote Similarity NPC604712
0.5577 Remote Similarity NPC31872
0.5536 Remote Similarity NPC141285
0.5357 Remote Similarity NPC246116
0.5179 Remote Similarity NPC11158

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC199100 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