Natural Product: NPC143659

Natural Product IDNPC143659
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3,3',5-Trihydroxybibenzyl
IUPAC Name 5-[2-(3-hydroxyphenyl)ethyl]benzene-1,3-diol
Synonyms 3,3',5-Trihydroxybibenzyl
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL479325
PubChem CID 21574990
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 UMZJVKFVOMTAFO-UHFFFAOYSA-N
Standard InCHI InChI=1S/C14H14O3/c15-12-3-1-2-10(6-12)4-5-11-7-13(16)9-14(17)8-11/h1-3,6-9,15-17H,4-5H2
SMILES Oc1cccc(c1)CCc1cc(O)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   230.09 Volume:   244.139
?
Van der Waals volume.
Dense:   0.942 LogP:   2.987
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.816
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.99
?
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:   2.046 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:   0.183 Fluc inhibitor:   0.309
?
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:   0.015
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.912 Promiscuous compounds:   0.404

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.832 MDCK Permeability:   -4.789
Pgp-inhibitor:   0.034 Pgp-substrate:   0.1
PAMPA:   0.269
?
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):   0.002
20% Bioavailability (F20%):   0.921 30% Bioavailability (F30%):   0.92
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.072 MRP1:   0.193
Plasma Protein Binding (PPB):   79.116% Volume Distribution (VD):   -0.083
Fu: 18.84%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.945
OATP1B3 inhibitor:   0.966 BCRP inhibitor:   0.294
BSEP inhibitor:   0.347

ADMET: Metabolism

CYP1A2-inhibitor:   0.987 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.146 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.998
CYP2D6-inhibitor:   0.95 CYP2D6-substrate:   0.605
CYP3A4-inhibitor:   0.214 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.118 CYP2C8-inhibitor:   1.0
HLM stability:   0.797
?
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):  10.523 Half-life (T1/2):  1.478

ADMET: Toxicity

hERG Blockers:  0.513 hERG Blockers (10um):  0.856
Human Hepatotoxicity (H-HT):  0.537 Drug-induced Liver Injury (DILI):  0.031
AMES Toxicity:  0.469 Rat Oral Acute Toxicity:  0.176
Maximum Recommended Daily Dose:  0.755 Skin Sensitization:  0.942
Carcinogencity:  0.256 Eye Corrosion:  0.469
Eye Irritation:  0.991 Respiratory Toxicity:  0.457
Drug-induced Neurotoxicity:  0.331 Ototoxicity:  0.328
Hematotoxicity:  0.066 Drug-induced Nephrotoxicity:  0.115
Genotoxicity:  0.795 RPMI-8226 Immunitoxicity:  0.049
A549 Cytotoxicity:  0.509 Hek293 Cytotoxicity:  0.901
BCF:   1.568
?
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:   4.058
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.999
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.627
?
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
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[11575955]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota stems Yunnan Province, China 2004 PMID[17253844]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems purchased from Kyoungdong Oriental Herbal Market, Seoul, Korea 2006-APR PMID[18052323]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems n.a. n.a. PMID[27310249]
NPO31139 Phalaenopsis sp. Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[7872785]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO3894 Dendrobium nobile 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT113 Cell line RAW264.7 Mus musculus Activity = 14.12 uM PMID[37852423]
NPT113 Cell line RAW264.7 Mus musculus Inhibition = 31.35 % PMID[37852423]
NPT113 Cell line RAW264.7 Mus musculus IC50 = 48220.0 nM PMID[37852423]
NPT113 Cell line RAW264.7 Mus musculus Activity = 110.02 % PMID[37852423]
NPT548 Tissue Ileum Cavia porcellus IC50 = 2360.0 nM PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Emax = 78.5 % PMID[14987052]
NPT548 Tissue Ileum Cavia porcellus Ratio IC50 = 1.78 n.a. PMID[14987052]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 > 10000.0 nM PMID[27310249]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC > 400000.0 nM PMID[27310249]
NPT610 Others Molecular identity unknown n.a. MIC = 217700.0 nM PMID[27310249]
NPT610 Others Molecular identity unknown n.a. MIC = 108700.0 nM PMID[27310249]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. MIC = 108700.0 nM PMID[27310249]
NPT610 Others Molecular identity unknown n.a. MIC = 217400.0 nM PMID[27310249]

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 NPC143659 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
0.84 Intermediate Similarity NPC599916
0.75 Intermediate Similarity NPC100340
0.75 Intermediate Similarity NPC609251
0.7241 Intermediate Similarity NPC274678
0.7 Intermediate Similarity NPC268032
0.6897 Remote Similarity NPC30506
0.6667 Remote Similarity NPC27974
0.6364 Remote Similarity NPC102216
0.6061 Remote Similarity NPC601800
0.5806 Remote Similarity NPC68055
0.5806 Remote Similarity NPC606762
0.5676 Remote Similarity NPC109828
0.5526 Remote Similarity NPC22610
0.5455 Remote Similarity NPC610566
0.5405 Remote Similarity NPC228922
0.5294 Remote Similarity NPC323810
0.5278 Remote Similarity NPC608070
0.525 Remote Similarity NPC247922
0.525 Remote Similarity NPC121115
0.5128 Remote Similarity NPC197757

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC143659 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