Natural Product: NPC246214

Natural Product IDNPC246214
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Dibenzofuran
IUPAC Name dibenzofuran
Synonyms Dibenzofuran
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL277497
PubChem CID 568
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000301] Benzofurans
        • [CHEMONTID:0000015] Dibenzofurans

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 TXCDCPKCNAJMEE-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H8O/c1-3-7-11-9(5-1)10-6-2-4-8-12(10)13-11/h1-8H
SMILES c1ccc2c(c1)oc1c2cccc1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   168.06 Volume:   183.41
?
Van der Waals volume.
Dense:   0.916 LogP:   3.946
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.598
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.558
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   15.0
TPSA:   13.14
?
Topological Polar Surface Area.
 H-Bond Acceptor:   1.0
H-Bond Donor:   0.0 Rings:   3.0
Heavy Atoms:   1.0

MedChem Properties

QED Drug-Likeness Score:   0.5 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.489 Fsp3:   0.0
MCE-18:   13.0
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Rejected
Pfizer Rule:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Accepted BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.161 Fluc inhibitor:   0.747
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.294
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.041
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.934 Promiscuous compounds:   0.929

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.376 MDCK Permeability:   -4.647
Pgp-inhibitor:   0.593 Pgp-substrate:   0.356
PAMPA:   0.148
?
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):   0.004
20% Bioavailability (F20%):   0.228 30% Bioavailability (F30%):   0.594
50% Bioavailability (F50%):   0.895

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.928 MRP1:   0.587
Plasma Protein Binding (PPB):   98.336% Volume Distribution (VD):   -0.049
Fu: 1.274%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.752
OATP1B3 inhibitor:   0.93 BCRP inhibitor:   0.717
BSEP inhibitor:   0.983

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.996
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.996
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.93
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.433
CYP3A4-inhibitor:   0.973 CYP3A4-substrate:   0.973
CYP2B6-substrate:   1.0 CYP2C8-inhibitor:   0.067
HLM stability:   0.997
?
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):  6.647 Half-life (T1/2):  1.354

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.509
Human Hepatotoxicity (H-HT):  0.578 Drug-induced Liver Injury (DILI):  0.859
AMES Toxicity:  0.682 Rat Oral Acute Toxicity:  0.498
Maximum Recommended Daily Dose:  0.349 Skin Sensitization:  0.405
Carcinogencity:  0.838 Eye Corrosion:  0.564
Eye Irritation:  0.987 Respiratory Toxicity:  0.67
Drug-induced Neurotoxicity:  0.282 Ototoxicity:  0.125
Hematotoxicity:  0.26 Drug-induced Nephrotoxicity:  0.134
Genotoxicity:  0.376 RPMI-8226 Immunitoxicity:  0.042
A549 Cytotoxicity:  0.1 Hek293 Cytotoxicity:  0.195
BCF:   3.047
?
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:   4.184
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.89
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.79
?
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
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[11374978]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[15679317]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota roots purchased from Kiu Shun Trading Ltd., Vancouver, Canada 2000 PMID[16643021]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. root n.a. PMID[17997069]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[20121210]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[25538068]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[27400088]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota Roots n.a. n.a. PMID[28558206]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. PMID[32031796]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[36838931]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. PMID[37480748]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2921 Angelica acutiloba Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO11438 Angelica gigas Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15890 Cimicifuga foetida Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2727 Actaea simplex Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8516 Dipsacus asperoides Species Caprifoliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15373 Actaea dahurica Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO389 Actaea heracleifolia Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15462 Angelica sinensis Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2921 Angelica acutiloba Species Apiaceae 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
NPT155 Individual protein Aryl hydrocarbon receptor Homo sapiens EC50 = 1000000.0 nM PMID[9435905]
NPT152 Individual protein Nuclear factor erythroid 2-related factor 2 Homo sapiens Potency n.a. 54482.7 nM PubChem BioAssay data set
NPT46 Individual protein Thyroid hormone receptor beta-1 Homo sapiens Potency n.a. 8912.5 nM PubChem BioAssay data set

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT3573 Organism Bovine viral diarrhea virus Bovine viral diarrhea virus 1 EC50 = 58000.0 nM PMID[18289862]
NPT2 Others Unspecified n.a. Potency n.a. 48557.7 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 76958.8 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 22199.3 nM PubChem BioAssay data set
NPT2 Others Unspecified n.a. Potency n.a. 69567.3 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
- Rattus norvegicus LOAEL = 12.3 mg/kg-day ToxVal
- Rattus norvegicus NOEL = 40.0 mg/kg-day ToxVal
- Rattus norvegicus NOAEL = 40.0 mg/kg-day ToxVal
- Homo sapiens RfD = 0.004 mg/kg-day ToxVal
- Homo sapiens RfD = 0.001 mg/kg-day ToxVal
- Homo sapiens RfD (provisional) = 0.004 mg/kg-day ToxVal
- Homo sapiens Medium-Specific Concentration = 4.5 mg/L ToxVal
- Homo sapiens Medium-Specific Concentration = 3.5 mg/L ToxVal
- Homo sapiens Medium-Specific Concentration = 0.097 mg/L ToxVal
- Homo sapiens Medium-Specific Concentration = 0.035 mg/L ToxVal
- Homo sapiens PAC-3 = 2000.0 mg/m3 ToxVal
- Homo sapiens PAC-2 = 330.0 mg/m3 ToxVal
- Homo sapiens PAC-1 = 30.0 mg/m3 ToxVal
- Homo sapiens MEG = 0.056 mg/L ToxVal
- Homo sapiens MEG = 673.0 mg/kg ToxVal
- Homo sapiens MEG = 30.0 mg/m3 ToxVal
- Homo sapiens MEG = 50.0 mg/m3 ToxVal
- Homo sapiens MEG = 250.0 mg/m3 ToxVal
- Homo sapiens RfD = 0.002 mg/kg-day ToxVal
- Homo sapiens RfD = 0.0016 mg/kg-day ToxVal

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 NPC246214 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
0.5357 Remote Similarity NPC475269
0.5357 Remote Similarity NPC35744

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC246214 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