Natural Product: NPC141090

Natural Product IDNPC141090
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,4'-Dihydroxy-5-Methoxybibenzyl
IUPAC Name 3-[2-(4-hydroxyphenyl)ethyl]-5-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL448371
PubChem CID 10014709
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 NSBYGUHECONSDC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C15H16O3/c1-18-15-9-12(8-14(17)10-15)3-2-11-4-6-13(16)7-5-11/h4-10,16-17H,2-3H2,1H3
SMILES COc1cc(CCc2ccc(cc2)O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   244.11 Volume:   261.435
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Van der Waals volume.
Dense:   0.934 LogP:   3.181
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.192
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.921
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   12.0
TPSA:   49.69
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.869 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.86 Fsp3:   0.2
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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.338 Fluc inhibitor:   0.394
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.019
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.21
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.866 Promiscuous compounds:   0.443

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.817 MDCK Permeability:   -4.795
Pgp-inhibitor:   0.07 Pgp-substrate:   0.031
PAMPA:   0.155
?
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%):   0.513 30% Bioavailability (F30%):   0.302
50% Bioavailability (F50%):   0.979

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.045 MRP1:   0.184
Plasma Protein Binding (PPB):   89.674% Volume Distribution (VD):   0.137
Fu: 11.527%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.996
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.076
BSEP inhibitor:   0.982

ADMET: Metabolism

CYP1A2-inhibitor:   0.976 CYP1A2-substrate:   0.963
CYP2C19-inhibitor:   0.913 CYP2C19-substrate:   0.607
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.989
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.997
CYP3A4-inhibitor:   0.002 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.077 CYP2C8-inhibitor:   0.999
HLM stability:   0.458
?
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):  12.612 Half-life (T1/2):  1.148

ADMET: Toxicity

hERG Blockers:  0.625 hERG Blockers (10um):  0.863
Human Hepatotoxicity (H-HT):  0.611 Drug-induced Liver Injury (DILI):  0.076
AMES Toxicity:  0.498 Rat Oral Acute Toxicity:  0.122
Maximum Recommended Daily Dose:  0.624 Skin Sensitization:  0.836
Carcinogencity:  0.305 Eye Corrosion:  0.441
Eye Irritation:  0.975 Respiratory Toxicity:  0.46
Drug-induced Neurotoxicity:  0.469 Ototoxicity:  0.387
Hematotoxicity:  0.138 Drug-induced Nephrotoxicity:  0.315
Genotoxicity:  0.212 RPMI-8226 Immunitoxicity:  0.062
A549 Cytotoxicity:  0.479 Hek293 Cytotoxicity:  0.836
BCF:   1.641
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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:   4.145
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.979
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.614
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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
NPO4606 Echium glomeratum Species Boraginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6162 Geigeria africana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6162 Geigeria africana Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1993 Helichrysum aphelexioides Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4606 Echium glomeratum Species Boraginaceae 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
NPT681 Cell line PC-12 Rattus norvegicus Activity = 12.08 % PMID[32711292]
NPT116 Cell line HL-60 Homo sapiens IC50 = 25600.0 nM PMID[32711292]
NPT548 Tissue Ileum Cavia porcellus IC50 = 140.0 nM PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Emax = 85.0 % PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Ratio IC50 = 30.85 n.a. PMID[14987052]
NPT2 Others Unspecified n.a. IC50 = 10100.0 nM PMID[14987052]
NPT2 Others Unspecified n.a. Activity = 45.3 % PMID[15043422]
NPT2 Others Unspecified n.a. Activity = 69.0 % PMID[15043422]

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 NPC141090 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
0.7838 Intermediate Similarity NPC276737
0.7632 Intermediate Similarity NPC22610
0.75 Intermediate Similarity NPC117214
0.7027 Intermediate Similarity NPC474933
0.7 Intermediate Similarity NPC53906
0.6905 Remote Similarity NPC150624
0.6829 Remote Similarity NPC282496
0.6829 Remote Similarity NPC116907
0.65 Remote Similarity NPC75440
0.6364 Remote Similarity NPC33270
0.6279 Remote Similarity NPC28765
0.6154 Remote Similarity NPC294327
0.6154 Remote Similarity NPC233526
0.6087 Remote Similarity NPC63574
0.5714 Remote Similarity NPC168657
0.5714 Remote Similarity NPC280606
0.5476 Remote Similarity NPC136319
0.5405 Remote Similarity NPC30506
0.5405 Remote Similarity NPC164576
0.5366 Remote Similarity NPC608070
0.5319 Remote Similarity NPC219070
0.5283 Remote Similarity NPC603965
0.5263 Remote Similarity NPC274678
0.5227 Remote Similarity NPC197757
0.5217 Remote Similarity NPC114064
0.5094 Remote Similarity NPC215588

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC141090 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