Natural Product: NPC221077

Natural Product IDNPC221077
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 5-(3-Methoxyphenethyl)-3-Methoxybenzene-1,2-Diol
IUPAC Name 3-methoxy-5-[2-(3-methoxyphenyl)ethyl]benzene-1,2-diol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL216090
PubChem CID 44418770
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 DEMRUANQYFMYPI-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H18O4/c1-19-13-5-3-4-11(8-13)6-7-12-9-14(17)16(18)15(10-12)20-2/h3-5,8-10,17-18H,6-7H2,1-2H3
SMILES COc1cccc(CCc2cc(c(c(c2)OC)O)O)c1

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   274.12 Volume:   287.521
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Van der Waals volume.
Dense:   0.953 LogP:   3.491
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.136
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.87
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The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   12.0
TPSA:   58.92
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Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.823 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   1.909 Fsp3:   0.25
MCE-18:   12.0
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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:   Accepted GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.363 Fluc inhibitor:   0.167
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.047
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.267
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.689 Promiscuous compounds:   0.431

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.089 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.984 Pgp-substrate:   0.031
PAMPA:   0.005
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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):   0.206
20% Bioavailability (F20%):   0.836 30% Bioavailability (F30%):   0.876
50% Bioavailability (F50%):   0.944

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.027 MRP1:   0.363
Plasma Protein Binding (PPB):   93.904% Volume Distribution (VD):   -0.342
Fu: 6.339%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.992
OATP1B3 inhibitor:   0.974 BCRP inhibitor:   0.718
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.99 CYP1A2-substrate:   0.754
CYP2C19-inhibitor:   0.992 CYP2C19-substrate:   0.607
CYP2C9-inhibitor:   1.0 CYP2C9-substrate:   0.338
CYP2D6-inhibitor:   0.978 CYP2D6-substrate:   0.983
CYP3A4-inhibitor:   0.802 CYP3A4-substrate:   0.936
CYP2B6-substrate:   0.107 CYP2C8-inhibitor:   1.0
HLM stability:   0.94
?
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):  12.898 Half-life (T1/2):  1.39

ADMET: Toxicity

hERG Blockers:  0.508 hERG Blockers (10um):  0.829
Human Hepatotoxicity (H-HT):  0.567 Drug-induced Liver Injury (DILI):  0.313
AMES Toxicity:  0.556 Rat Oral Acute Toxicity:  0.143
Maximum Recommended Daily Dose:  0.474 Skin Sensitization:  0.874
Carcinogencity:  0.324 Eye Corrosion:  0.195
Eye Irritation:  0.921 Respiratory Toxicity:  0.545
Drug-induced Neurotoxicity:  0.325 Ototoxicity:  0.645
Hematotoxicity:  0.273 Drug-induced Nephrotoxicity:  0.418
Genotoxicity:  0.072 RPMI-8226 Immunitoxicity:  0.054
A549 Cytotoxicity:  0.661 Hek293 Cytotoxicity:  0.482
BCF:   1.608
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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:   4.142
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.449
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.867
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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
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. PMID[11575955]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[16268553]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. Fijian red alga n.a. PMID[16724831]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota stems Yunnan Province, China 2004 PMID[17253844]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[17715978]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems purchased from Kyoungdong Oriental Herbal Market, Seoul, Korea 2006-APR PMID[18052323]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. Fijian red alga n.a. PMID[20141173]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota Stems n.a. n.a. PMID[27310249]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. PMID[30407005]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15662 Ligustrum ovalifolium Species Oleaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13053 Corydalis conspersa Species Papaveraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1575 Mikania luetzelburgii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO326 Pittosporum brevicalyx Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15280 Sideritis grandiflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO6178 Solanum euacanthum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4581 Ungernia victoris Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. Database[FooDB]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota Fruits n.a. Database[Phenol-Explorer]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
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]
NPO8966 Callophycus serratus Species Solieriaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO6178 Solanum euacanthum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1575 Mikania luetzelburgii Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO5019 Mespilus germanica Species Rosaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15280 Sideritis grandiflora Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO4581 Ungernia victoris Species Amaryllidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11242 Gynochthodes parvifolia Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15662 Ligustrum ovalifolium Species Oleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO326 Pittosporum brevicalyx Species Pittosporaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3894 Dendrobium nobile Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13053 Corydalis conspersa Species Papaveraceae 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
NPT28833 No target No relevant target n.a. IC50 = 40300.0 nM PMID[32711292]
NPT1 Others Radical scavenging activity n.a. IC50 = 40300.0 nM PMID[17253844]

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 NPC221077 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
0.6744 Remote Similarity NPC53906
0.6667 Remote Similarity NPC299028
0.6279 Remote Similarity NPC75440
0.5854 Remote Similarity NPC233599
0.5854 Remote Similarity NPC2682
0.5217 Remote Similarity NPC276737
0.5106 Remote Similarity NPC22610
0.5102 Remote Similarity NPC117214

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC221077 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