Natural Product: NPC102216

Natural Product IDNPC102216
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 2',3,5-Trihydroxybibenzyl
IUPAC Name 5-[2-(2-hydroxyphenyl)ethyl]benzene-1,3-diol
Synonyms 2',3,5-Trihydroxybibenzyl
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL474628
PubChem CID 442699
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 QNLYZTMYRVYPMN-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H14O3/c15-12-7-10(8-13(16)9-12)5-6-11-3-1-2-4-14(11)17/h1-4,7-9,15-17H,5-6H2
SMILES Oc1cc(CCc2ccccc2O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   230.09 Volume:   244.139
?
Van der Waals volume.
Dense:   0.942 LogP:   2.967
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.638
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.121
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   60.69
?
Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.759 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.052 Fsp3:   0.143
MCE-18:   11.0
?
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:   0.231 Fluc inhibitor:   0.092
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.014
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.931 Promiscuous compounds:   0.396

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.845 MDCK Permeability:   -4.808
Pgp-inhibitor:   0.0 Pgp-substrate:   0.01
PAMPA:   0.671
?
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%):   0.93 30% Bioavailability (F30%):   0.949
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.019 MRP1:   0.473
Plasma Protein Binding (PPB):   83.852% Volume Distribution (VD):   0.188
Fu: 14.789%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.958
OATP1B3 inhibitor:   0.964 BCRP inhibitor:   0.007
BSEP inhibitor:   0.105

ADMET: Metabolism

CYP1A2-inhibitor:   0.99 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.225 CYP2C19-substrate:   0.999
CYP2C9-inhibitor:   0.997 CYP2C9-substrate:   0.984
CYP2D6-inhibitor:   0.998 CYP2D6-substrate:   0.387
CYP3A4-inhibitor:   0.5 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.12 CYP2C8-inhibitor:   1.0
HLM stability:   0.971
?
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):  9.872 Half-life (T1/2):  1.432

ADMET: Toxicity

hERG Blockers:  0.376 hERG Blockers (10um):  0.84
Human Hepatotoxicity (H-HT):  0.551 Drug-induced Liver Injury (DILI):  0.025
AMES Toxicity:  0.47 Rat Oral Acute Toxicity:  0.178
Maximum Recommended Daily Dose:  0.681 Skin Sensitization:  0.945
Carcinogencity:  0.174 Eye Corrosion:  0.558
Eye Irritation:  0.99 Respiratory Toxicity:  0.646
Drug-induced Neurotoxicity:  0.15 Ototoxicity:  0.305
Hematotoxicity:  0.066 Drug-induced Nephrotoxicity:  0.194
Genotoxicity:  0.579 RPMI-8226 Immunitoxicity:  0.07
A549 Cytotoxicity:  0.608 Hek293 Cytotoxicity:  0.877
BCF:   1.366
?
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:   3.918
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.084
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.574
?
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
NPO20097 Thermobifida alba Species Nocardiopsaceae Bacteria n.a. n.a. n.a. PMID[11430001]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota aerial parts n.a. n.a. PMID[16124773]
NPO9419 Enterobacter cloacae Species Enterobacteriaceae Bacteria n.a. n.a. n.a. PMID[25427277]
NPO24359 Streptomyces cacaoi Species Streptomycetaceae Bacteria n.a. n.a. n.a. PMID[27642865]
NPO26245 Styracaster caroli Species Porcellanasteridae Eukaryota n.a. n.a. n.a. PMID[8145229]
NPO13147 Euphorbia cyparissias Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9419 Enterobacter cloacae Species Enterobacteriaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO20097 Thermobifida alba Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO26245 Styracaster caroli Species Porcellanasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8559 Calophyllum venulosum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11319 Laurencia hybrida Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24359 Streptomyces cacaoi Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO24359 Streptomyces cacaoi Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO7863 Dioscorea opposita Species Dioscoreaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9419 Enterobacter cloacae Species Enterobacteriaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO20097 Thermobifida alba Species Nocardiopsaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO13147 Euphorbia cyparissias Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19605 Tara spinosa Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8460 Pedicularis torta Species Orobanchaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11181 Juniperus bermudiana Species Cupressaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6962 Cetraria delisei Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11319 Laurencia hybrida Species Rhodomelaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8559 Calophyllum venulosum Species Calophyllaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10024 Tylecodon wallichii Species Crassulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6054 Sinularia brongersmai Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26245 Styracaster caroli Species Porcellanasteridae 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
NPT325 Individual protein Cyclooxygenase-2 Ovis aries IC50 = 19.5 ug.mL-1 PMID[19303782]
NPT324 Individual protein Cyclooxygenase-1 Ovis aries IC50 > 100.0 ug.mL-1 PMID[19303782]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 100.0 ug.mL-1 PMID[19303782]
NPT1 Others Radical scavenging activity n.a. IC50 > 100.0 ug.mL-1 PMID[19303782]
NPT2 Others Unspecified n.a. Ratio IC50 > 5.1 n.a. PMID[19303782]

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 NPC102216 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
0.7273 Intermediate Similarity NPC601800
0.6562 Remote Similarity NPC100340
0.6364 Remote Similarity NPC143659
0.6061 Remote Similarity NPC30506
0.5952 Remote Similarity NPC150624
0.5714 Remote Similarity NPC268032
0.5484 Remote Similarity NPC307235
0.5366 Remote Similarity NPC105925
0.5366 Remote Similarity NPC69261
0.5366 Remote Similarity NPC293054
0.5227 Remote Similarity NPC246620
0.5227 Remote Similarity NPC184302
0.5152 Remote Similarity NPC599916
0.5143 Remote Similarity NPC609251
0.5116 Remote Similarity NPC225679

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC102216 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