Natural Product: NPC470804

Natural Product IDNPC470804
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-O-Ethylguaiacylglycerol
IUPAC Name 3-ethoxy-3-(4-hydroxy-3-methoxyphenyl)propane-1,2-diol
Synonyms 7-O-Ethylguaiacylglycerol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL224843
PubChem CID 44421292
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000134] Phenols
        • [CHEMONTID:0000190] Methoxyphenols

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 AAOACSSPCZAJCZ-UHFFFAOYSA-N
Standard InCHI InChI=1S/C12H18O5/c1-3-17-12(10(15)7-13)8-4-5-9(14)11(6-8)16-2/h4-6,10,12-15H,3,7H2,1-2H3
SMILES CCOC(c1ccc(c(c1)OC)O)C(CO)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   242.12 Volume:   243.594
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Van der Waals volume.
Dense:   0.994 LogP:   0.403
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.485
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.193
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   6.0
TPSA:   79.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   3.0 Rings:   1.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.688 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.114 Fsp3:   0.5
MCE-18:   16.0
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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:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.131 Fluc inhibitor:   0.0
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.014
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.154
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.302 Promiscuous compounds:   0.355

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.825 MDCK Permeability:   -4.567
Pgp-inhibitor:   0.003 Pgp-substrate:   0.032
PAMPA:   0.477
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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):   0.217
20% Bioavailability (F20%):   0.21 30% Bioavailability (F30%):   0.786
50% Bioavailability (F50%):   0.898

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.129 MRP1:   0.574
Plasma Protein Binding (PPB):   55.686% Volume Distribution (VD):   0.011
Fu: 46.815%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.989
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.34
BSEP inhibitor:   0.059

ADMET: Metabolism

CYP1A2-inhibitor:   0.004 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.01 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.633 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.224 CYP2D6-substrate:   0.066
CYP3A4-inhibitor:   0.022 CYP3A4-substrate:   0.02
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.23
HLM stability:   0.021
?
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):  8.16 Half-life (T1/2):  1.568

ADMET: Toxicity

hERG Blockers:  0.056 hERG Blockers (10um):  0.455
Human Hepatotoxicity (H-HT):  0.312 Drug-induced Liver Injury (DILI):  0.075
AMES Toxicity:  0.468 Rat Oral Acute Toxicity:  0.088
Maximum Recommended Daily Dose:  0.127 Skin Sensitization:  0.354
Carcinogencity:  0.331 Eye Corrosion:  0.015
Eye Irritation:  0.861 Respiratory Toxicity:  0.085
Drug-induced Neurotoxicity:  0.151 Ototoxicity:  0.732
Hematotoxicity:  0.1 Drug-induced Nephrotoxicity:  0.173
Genotoxicity:  0.01 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.079 Hek293 Cytotoxicity:  0.165
BCF:   0.299
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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:   2.405
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.782
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.048
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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
NPO14922 Tarenna attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[16792422]
NPO14922 Tarenna attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. PMID[17343407]
NPO14922 Tarenna attenuata Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14922 Tarenna attenuata Species Rubiaceae 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 = 54.1 % PubChem BioAssay data set
NPT681 Cell line PC-12 Rattus norvegicus Activity = 54.9 % PMID[24694055]
NPT681 Cell line PC-12 Rattus norvegicus Activity = 56.8 % PMID[24694055]
NPT681 Cell line PC-12 Rattus norvegicus Activity = 57.3 % PMID[25554367]
NPT1 Others Radical scavenging activity n.a. IC50 = 132000.0 nM PMID[19848432]

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 NPC470804 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
0.625 Remote Similarity NPC469480
0.5833 Remote Similarity NPC4940
0.5745 Remote Similarity NPC209567
0.5741 Remote Similarity NPC480701
0.5625 Remote Similarity NPC115207
0.5625 Remote Similarity NPC158079
0.5625 Remote Similarity NPC228346
0.5625 Remote Similarity NPC242807
0.5625 Remote Similarity NPC40432
0.5625 Remote Similarity NPC161557
0.5625 Remote Similarity NPC153739
0.5532 Remote Similarity NPC282703
0.5532 Remote Similarity NPC184733
0.5532 Remote Similarity NPC128208
0.5532 Remote Similarity NPC129570
0.5532 Remote Similarity NPC63238
0.5532 Remote Similarity NPC602603
0.5532 Remote Similarity NPC606519
0.5472 Remote Similarity NPC478955
0.5472 Remote Similarity NPC478700
0.5306 Remote Similarity NPC142985
0.5294 Remote Similarity NPC147379
0.5263 Remote Similarity NPC135127
0.5192 Remote Similarity NPC126409
0.5192 Remote Similarity NPC99572
0.5106 Remote Similarity NPC255675

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC470804 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