Natural Product: NPC63574

Natural Product IDNPC63574
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 3-[2-(1,3-Benzodioxol-5-Yl)Ethyl]-5-Methoxyphenol
IUPAC Name 3-[2-(1,3-benzodioxol-5-yl)ethyl]-5-methoxyphenol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1796012
PubChem CID 637412
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 WXLWYVQONUUBMT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H16O4/c1-18-14-7-12(6-13(17)9-14)3-2-11-4-5-15-16(8-11)20-10-19-15/h4-9,17H,2-3,10H2,1H3
SMILES COc1cc(CCc2ccc3c(c2)OCO3)cc(c1)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.1 Volume:   278.965
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Van der Waals volume.
Dense:   0.975 LogP:   3.542
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.36
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.629
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   16.0
TPSA:   47.92
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.929 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.046 Fsp3:   0.25
MCE-18:   31.5
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.426 Fluc inhibitor:   0.369
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.107
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.394
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.461 Promiscuous compounds:   0.401

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.97 MDCK Permeability:   -4.739
Pgp-inhibitor:   0.766 Pgp-substrate:   0.007
PAMPA:   0.025
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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):   0.001
20% Bioavailability (F20%):   0.257 30% Bioavailability (F30%):   0.009
50% Bioavailability (F50%):   0.832

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.564 MRP1:   0.125
Plasma Protein Binding (PPB):   96.97% Volume Distribution (VD):   0.201
Fu: 3.324%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.99
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.101
BSEP inhibitor:   1.0

ADMET: Metabolism

CYP1A2-inhibitor:   1.0 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   1.0 CYP2C19-substrate:   0.96
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   1.0
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.197 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.992 CYP2C8-inhibitor:   0.999
HLM stability:   0.954
?
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):  7.179 Half-life (T1/2):  0.954

ADMET: Toxicity

hERG Blockers:  0.575 hERG Blockers (10um):  0.795
Human Hepatotoxicity (H-HT):  0.631 Drug-induced Liver Injury (DILI):  0.311
AMES Toxicity:  0.616 Rat Oral Acute Toxicity:  0.156
Maximum Recommended Daily Dose:  0.634 Skin Sensitization:  0.662
Carcinogencity:  0.552 Eye Corrosion:  0.212
Eye Irritation:  0.927 Respiratory Toxicity:  0.562
Drug-induced Neurotoxicity:  0.498 Ototoxicity:  0.436
Hematotoxicity:  0.336 Drug-induced Nephrotoxicity:  0.462
Genotoxicity:  0.267 RPMI-8226 Immunitoxicity:  0.098
A549 Cytotoxicity:  0.343 Hek293 Cytotoxicity:  0.685
BCF:   1.942
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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:   4.235
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.547
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.941
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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
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO29285 Dendrobium densiflorum Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO29285 Dendrobium densiflorum 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
NPT1621 Individual protein Calmodulin Homo sapiens IC50 = 31290.0 nM PMID[21514702]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC63574 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
0.7907 Intermediate Similarity NPC282496
0.6591 Remote Similarity NPC604144
0.6522 Remote Similarity NPC53906
0.6383 Remote Similarity NPC116907
0.6087 Remote Similarity NPC276737
0.6087 Remote Similarity NPC141090
0.5957 Remote Similarity NPC22610
0.5918 Remote Similarity NPC117214
0.5745 Remote Similarity NPC608982
0.5686 Remote Similarity NPC33270
0.5556 Remote Similarity NPC608195
0.549 Remote Similarity NPC150624
0.5333 Remote Similarity NPC31279
0.5294 Remote Similarity NPC28765
0.5102 Remote Similarity NPC470626
0.5094 Remote Similarity NPC249788
0.5088 Remote Similarity NPC112237
0.5085 Remote Similarity NPC234152

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC63574 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