Natural Product: NPC114155

Natural Product IDNPC114155
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-Hydroxy-6'-O-Desmethylterphenyllin
IUPAC Name 2-(3,4-dihydroxyphenyl)-5-(4-hydroxyphenyl)-4-methoxybenzene-1,3-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1801783
PubChem CID 53262758
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0002042] Terphenyls
          • [CHEMONTID:0002126] P-terphenyls

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 ATMBBZRMOGOHOQ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H16O6/c1-25-19-13(10-2-5-12(20)6-3-10)9-16(23)17(18(19)24)11-4-7-14(21)15(22)8-11/h2-9,20-24H,1H3
SMILES COc1c(cc(c(c1O)c1ccc(c(c1)O)O)O)c1ccc(cc1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   340.09 Volume:   340.524
?
Van der Waals volume.
Dense:   0.999 LogP:   3.092
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.055
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.272
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   18.0
TPSA:   110.38
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.466 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.359 Fsp3:   0.053
MCE-18:   19.0
?
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:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.93 Fluc inhibitor:   0.456
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.683
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.24
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.682 Promiscuous compounds:   0.724

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.27 MDCK Permeability:   -4.833
Pgp-inhibitor:   0.0 Pgp-substrate:   0.002
PAMPA:   0.999
?
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):   0.062
20% Bioavailability (F20%):   0.827 30% Bioavailability (F30%):   0.46
50% Bioavailability (F50%):   0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.001 MRP1:   0.936
Plasma Protein Binding (PPB):   88.195% Volume Distribution (VD):   -0.377
Fu: 11.921%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.978
OATP1B3 inhibitor:   0.959 BCRP inhibitor:   0.011
BSEP inhibitor:   0.023

ADMET: Metabolism

CYP1A2-inhibitor:   0.167 CYP1A2-substrate:   0.186
CYP2C19-inhibitor:   0.001 CYP2C19-substrate:   0.161
CYP2C9-inhibitor:   0.149 CYP2C9-substrate:   0.046
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.984
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.336
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.972
HLM stability:   0.745
?
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):  5.328 Half-life (T1/2):  1.87

ADMET: Toxicity

hERG Blockers:  0.128 hERG Blockers (10um):  0.757
Human Hepatotoxicity (H-HT):  0.483 Drug-induced Liver Injury (DILI):  0.284
AMES Toxicity:  0.486 Rat Oral Acute Toxicity:  0.4
Maximum Recommended Daily Dose:  0.726 Skin Sensitization:  0.975
Carcinogencity:  0.411 Eye Corrosion:  0.018
Eye Irritation:  0.983 Respiratory Toxicity:  0.666
Drug-induced Neurotoxicity:  0.084 Ototoxicity:  0.541
Hematotoxicity:  0.052 Drug-induced Nephrotoxicity:  0.091
Genotoxicity:  0.771 RPMI-8226 Immunitoxicity:  0.043
A549 Cytotoxicity:  0.907 Hek293 Cytotoxicity:  0.755
BCF:   1.208
?
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:   4.061
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.766
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.369
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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
NPO9828 Penicillium chermesinum Species Aspergillaceae Eukaryota isolated from the stem of the mangrove plant Kandelia candel South China Sea in Guangdong Province, China n.a. PMID[21510637]
NPO9828 Penicillium chermesinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21510637]
NPO8113 Streptomyces murayamaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO7400 Marsdenia cundurango Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9828 Penicillium chermesinum Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1216 Aesculus indica Species Hippocastanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO7400 Marsdenia cundurango Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8113 Streptomyces murayamaensis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO11924 Sesuvium portulaca Species Aizoaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9828 Penicillium chermesinum Species Aspergillaceae 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
NPT66 Individual protein Acetylcholinesterase Electrophorus electricus IC50 > 100000.0 nM PMID[21510637]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT28897 Organism Human alphaherpesvirus 1 Human alphaherpesvirus 1 EC50 = 1800.0 nM PMID[34766503]
NPT30043 Cell line Vero Chlorocebus sabaeus CC50 > 100000.0 nM PMID[34766503]
NPT2 Others Unspecified n.a. IC50 = 4900.0 nM PMID[21510637]
NPT30145 Organism Human alphaherpesvirus 2 Human alphaherpesvirus 2 EC50 = 2300.0 nM PMID[34766503]

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 NPC114155 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
0.8889 High Similarity NPC6262
0.8611 High Similarity NPC300846
0.6136 Remote Similarity NPC272157
0.5333 Remote Similarity NPC201145
0.5227 Remote Similarity NPC90615
0.5208 Remote Similarity NPC73535

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC114155 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