Natural Product: NPC116838

Natural Product IDNPC116838
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 9-(3,4-Dimethoxyphenyl)-5-Hydroxy-6H-[2]Benzofuro[5,6-F][1,3]Benzodioxol-8-One
IUPAC Name 9-(3,4-dimethoxyphenyl)-5-hydroxy-6H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL495476
PubChem CID 332529
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0001392] Lignans, neolignans and related compounds
      • [CHEMONTID:0001610] Arylnaphthalene lignans

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 ZYUVOQCJYNAWNV-UHFFFAOYSA-N
Standard InCHI InChI=1S/C21H16O7/c1-24-14-4-3-10(5-15(14)25-2)18-11-6-16-17(28-9-27-16)7-12(11)20(22)13-8-26-21(23)19(13)18/h3-7,22H,8-9H2,1-2H3
SMILES COc1ccc(cc1OC)c1c2cc3c(cc2c(c2COC(=O)c12)O)OCO3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   380.09 Volume:   366.793
?
Van der Waals volume.
Dense:   1.036 LogP:   2.894
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.76
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.319
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The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   26.0
TPSA:   83.45
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.695 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.616 Fsp3:   0.19
MCE-18:   58.32
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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:   0.829 Fluc inhibitor:   0.078
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.788
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.39
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.222 Promiscuous compounds:   0.732

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.978 MDCK Permeability:   -4.708
Pgp-inhibitor:   0.337 Pgp-substrate:   0.06
PAMPA:   0.365
?
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):   0.276
20% Bioavailability (F20%):   0.203 30% Bioavailability (F30%):   0.037
50% Bioavailability (F50%):   0.556

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.016 MRP1:   0.835
Plasma Protein Binding (PPB):   96.023% Volume Distribution (VD):   -0.188
Fu: 4.058%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.902
OATP1B3 inhibitor:   0.98 BCRP inhibitor:   0.275
BSEP inhibitor:   0.992

ADMET: Metabolism

CYP1A2-inhibitor:   0.997 CYP1A2-substrate:   0.776
CYP2C19-inhibitor:   0.999 CYP2C19-substrate:   0.727
CYP2C9-inhibitor:   0.987 CYP2C9-substrate:   0.832
CYP2D6-inhibitor:   0.999 CYP2D6-substrate:   0.986
CYP3A4-inhibitor:   0.903 CYP3A4-substrate:   0.924
CYP2B6-substrate:   0.963 CYP2C8-inhibitor:   0.047
HLM stability:   0.468
?
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):  4.816 Half-life (T1/2):  1.375

ADMET: Toxicity

hERG Blockers:  0.196 hERG Blockers (10um):  0.633
Human Hepatotoxicity (H-HT):  0.874 Drug-induced Liver Injury (DILI):  0.983
AMES Toxicity:  0.92 Rat Oral Acute Toxicity:  0.662
Maximum Recommended Daily Dose:  0.916 Skin Sensitization:  0.971
Carcinogencity:  0.983 Eye Corrosion:  0.0
Eye Irritation:  0.523 Respiratory Toxicity:  0.652
Drug-induced Neurotoxicity:  0.788 Ototoxicity:  0.619
Hematotoxicity:  0.928 Drug-induced Nephrotoxicity:  0.97
Genotoxicity:  0.962 RPMI-8226 Immunitoxicity:  0.384
A549 Cytotoxicity:  0.707 Hek293 Cytotoxicity:  0.782
BCF:   1.435
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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:   4.069
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.736
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.934
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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
NPO16896 Justicia ciliata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[10425143]
NPO16896 Justicia ciliata Species Acanthaceae Eukaryota n.a. n.a. n.a. PMID[11087610]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16896 Justicia ciliata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO20518 Polygala chinensis Species Polygalaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO1484 Bupleurum scorzonerifolium Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16896 Justicia ciliata Species Acanthaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20518 Polygala chinensis 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT71 Cell line HEK293 Homo sapiens IC50 = 81900.0 nM DOI[10.1007/s00044-011-9937-1]
NPT91 Cell line KB Homo sapiens IC50 = 45200.0 nM DOI[10.1007/s00044-011-9937-1]
NPT660 Cell line SW480 Homo sapiens IC50 > 100000.0 nM DOI[10.1007/s00044-011-9937-1]
NPT81 Cell line A549 Homo sapiens IC50 = 39500.0 nM DOI[10.1007/s00044-011-9937-1]
NPT2428 Cell line HT-3 Homo sapiens IC50 > 10.0 ug.mL-1 PMID[30830783]

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 NPC116838 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
0.8929 High Similarity NPC22130
0.8909 High Similarity NPC198796
0.8246 Intermediate Similarity NPC174734
0.7797 Intermediate Similarity NPC117911
0.6562 Remote Similarity NPC474042
0.6508 Remote Similarity NPC115123
0.6 Remote Similarity NPC19600
0.5758 Remote Similarity NPC239113
0.5758 Remote Similarity NPC299820
0.5692 Remote Similarity NPC181464
0.5441 Remote Similarity NPC15212
0.5303 Remote Similarity NPC234730
0.5224 Remote Similarity NPC473900
0.5217 Remote Similarity NPC127827
0.5217 Remote Similarity NPC78944
0.5147 Remote Similarity NPC24193

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC116838 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