Natural Product: NPC114392

Natural Product IDNPC114392
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (E)-5-(3,5-Dihydroxystyryl)Benzene-1,2,3-Triol
IUPAC Name 5-[(E)-2-(3,5-dihydroxyphenyl)ethenyl]benzene-1,2,3-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL2260735
PubChem CID 9859982
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes

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 PBRNOKNVNSKDQZ-OWOJBTEDSA-N
Standard InCHI InChI=1S/C14H12O5/c15-10-3-8(4-11(16)7-10)1-2-9-5-12(17)14(19)13(18)6-9/h1-7,15-19H/b2-1+
SMILES Oc1cc(/C=C/c2cc(O)c(c(c2)O)O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   260.07 Volume:   259.083
?
Van der Waals volume.
Dense:   1.004 LogP:   1.91
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.039
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.612
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   13.0
TPSA:   101.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.421 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.498 Fsp3:   0.0
MCE-18:   13.0
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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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.883 Fluc inhibitor:   1.0
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.021
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.102
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.841 Promiscuous compounds:   0.898

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.54 MDCK Permeability:   -4.898
Pgp-inhibitor:   0.0 Pgp-substrate:   0.001
PAMPA:   0.809
?
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):   0.001
20% Bioavailability (F20%):   0.95 30% Bioavailability (F30%):   0.967
50% Bioavailability (F50%):   0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.684
Plasma Protein Binding (PPB):   82.519% Volume Distribution (VD):   -0.287
Fu: 18.665%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.999 BCRP inhibitor:   0.38
BSEP inhibitor:   0.001

ADMET: Metabolism

CYP1A2-inhibitor:   0.033 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.189 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.014
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.778
?
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):  9.0 Half-life (T1/2):  1.969

ADMET: Toxicity

hERG Blockers:  0.163 hERG Blockers (10um):  0.833
Human Hepatotoxicity (H-HT):  0.578 Drug-induced Liver Injury (DILI):  0.286
AMES Toxicity:  0.734 Rat Oral Acute Toxicity:  0.329
Maximum Recommended Daily Dose:  0.946 Skin Sensitization:  0.999
Carcinogencity:  0.35 Eye Corrosion:  0.043
Eye Irritation:  0.997 Respiratory Toxicity:  0.442
Drug-induced Neurotoxicity:  0.007 Ototoxicity:  0.685
Hematotoxicity:  0.011 Drug-induced Nephrotoxicity:  0.009
Genotoxicity:  0.995 RPMI-8226 Immunitoxicity:  0.009
A549 Cytotoxicity:  0.976 Hek293 Cytotoxicity:  0.734
BCF:   0.761
?
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:   3.158
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.553
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.138
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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
NPO6294 Trinia scabra Species Apiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9149 Phalaenopsis cornu-cervi Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4110 Lentzea albida Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO23933 Gymnosporia diversifolia Species Celastraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5100 Fritillaria persica Species Liliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11809 Eleutherococcus sessiliflorus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7749 Coprosma lucida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18961 Azotobacter agilis Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO11809 Eleutherococcus sessiliflorus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO7749 Coprosma lucida Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5100 Fritillaria persica Species Liliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11809 Eleutherococcus sessiliflorus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6294 Trinia scabra Species Apiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18961 Azotobacter agilis Species Pseudomonadaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO23933 Gymnosporia diversifolia Species Celastraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4110 Lentzea albida Species Pseudonocardiaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO9149 Phalaenopsis cornu-cervi Species Orchidaceae 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
NPT346 Individual protein Transient receptor potential cation channel subfamily A member 1 Homo sapiens FC = 0.4 n.a. PMID[28576617]
NPT346 Individual protein Transient receptor potential cation channel subfamily A member 1 Homo sapiens FC = 0.3 n.a. PMID[28576617]
NPT24816 Single protein Alpha-mannosidase Canavalia ensiformis Inhibition < 50.0 % PMID[31927314]
NPT496 Individual protein Alpha-L-fucosidase 1 Bos taurus Inhibition < 50.0 % PMID[31927314]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28438 Unchecked Unchecked n.a. IC50 = 19000.0 nM PMID[35367706]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. TIME = 48.1 hr DOI[10.1007/s00044-009-9236-2]
NPT1 Others Radical scavenging activity n.a. Inhibition = 92.9 % DOI[10.1007/s00044-009-9236-2]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 12.1 % PMID[35367706]





 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 NPC114392 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
0.6897 Remote Similarity NPC34864
0.6897 Remote Similarity NPC105727
0.6897 Remote Similarity NPC58427
0.6207 Remote Similarity NPC176527
0.6207 Remote Similarity NPC291789
0.6207 Remote Similarity NPC248573
0.6207 Remote Similarity NPC161571
0.6207 Remote Similarity NPC275053
0.5455 Remote Similarity NPC292452
0.5455 Remote Similarity NPC61516
0.5294 Remote Similarity NPC261343
0.5143 Remote Similarity NPC296920
0.5143 Remote Similarity NPC90520

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC114392 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
0.6207 Remote Similarity NPD1242 Phase 3

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