Natural Product: NPC473408

Natural Product IDNPC473408
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (-)-5-Methoxybalanophonin
IUPAC Name (E)-3-[(2S,3R)-2-(4-hydroxy-3,5-dimethoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]prop-2-enal
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL413991
PubChem CID 44445794
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0003405] 2-arylbenzofuran flavonoids

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 YJXKBHCATWSLFQ-BMSLLPBFSA-N
Standard InCHI InChI=1S/C21H22O7/c1-25-16-9-13(10-17(26-2)19(16)24)20-15(11-23)14-7-12(5-4-6-22)8-18(27-3)21(14)28-20/h4-10,15,20,23-24H,11H2,1-3H3/b5-4+/t15-,20+/m0/s1
SMILES COC1=CC(=CC2=C1OC(C2CO)C3=CC(=C(C(=C3)OC)O)OC)C=CC=O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   386.14 Volume:   386.543
?
Van der Waals volume.
Dense:   0.999 LogP:   1.987
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.33
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.784
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   94.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.558 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.537 Fsp3:   0.286
MCE-18:   59.815
?
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:   0
Colloidal aggregators:   0.536 Fluc inhibitor:   0.334
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.099
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.628
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.342 Promiscuous compounds:   0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.449 MDCK Permeability:   -5.085
Pgp-inhibitor:   0.932 Pgp-substrate:   0.111
PAMPA:   0.018
?
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):   0.051
20% Bioavailability (F20%):   0.165 30% Bioavailability (F30%):   0.13
50% Bioavailability (F50%):   0.952

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.125 MRP1:   0.955
Plasma Protein Binding (PPB):   91.53% Volume Distribution (VD):   -0.179
Fu: 7.409%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.951
BSEP inhibitor:   0.991

ADMET: Metabolism

CYP1A2-inhibitor:   0.677 CYP1A2-substrate:   0.659
CYP2C19-inhibitor:   0.932 CYP2C19-substrate:   0.308
CYP2C9-inhibitor:   0.968 CYP2C9-substrate:   0.038
CYP2D6-inhibitor:   0.549 CYP2D6-substrate:   0.635
CYP3A4-inhibitor:   0.209 CYP3A4-substrate:   0.72
CYP2B6-substrate:   0.003 CYP2C8-inhibitor:   0.964
HLM stability:   0.252
?
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):  6.366 Half-life (T1/2):  1.878

ADMET: Toxicity

hERG Blockers:  0.135 hERG Blockers (10um):  0.483
Human Hepatotoxicity (H-HT):  0.56 Drug-induced Liver Injury (DILI):  0.203
AMES Toxicity:  0.725 Rat Oral Acute Toxicity:  0.565
Maximum Recommended Daily Dose:  0.359 Skin Sensitization:  0.965
Carcinogencity:  0.578 Eye Corrosion:  0.022
Eye Irritation:  0.848 Respiratory Toxicity:  0.497
Drug-induced Neurotoxicity:  0.708 Ototoxicity:  0.691
Hematotoxicity:  0.147 Drug-induced Nephrotoxicity:  0.606
Genotoxicity:  0.101 RPMI-8226 Immunitoxicity:  0.169
A549 Cytotoxicity:  0.201 Hek293 Cytotoxicity:  0.189
BCF:   1.037
?
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:   3.661
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.255
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.61
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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
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota fruit Lanyu Island, Taitung County, Taiwan n.a. PMID[10395498]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. PMID[17822293]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO21390 Zanthoxylum integrifoliolum Species Rutaceae 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
NPT2740 Cell line Neutrophils n.a. IC50 = 19300.0 nM PMID[10843591]
NPT65 Cell line HepG2 Homo sapiens IC50 = 88700.0 nM PMID[29567344]
NPT20904 Cell line Hep 3B2 Homo sapiens IC50 = 72800.0 nM PMID[29567344]

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 NPC473408 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
0.8333 Intermediate Similarity NPC87725
0.8333 Intermediate Similarity NPC263261
0.8246 Intermediate Similarity NPC284881
0.8246 Intermediate Similarity NPC93433
0.8246 Intermediate Similarity NPC474444
0.7 Intermediate Similarity NPC156502
0.7 Intermediate Similarity NPC10737
0.6562 Remote Similarity NPC206413
0.6562 Remote Similarity NPC482649
0.6562 Remote Similarity NPC149003
0.6562 Remote Similarity NPC482647
0.6562 Remote Similarity NPC482648
0.6562 Remote Similarity NPC482651
0.6562 Remote Similarity NPC194244
0.6562 Remote Similarity NPC482650
0.6552 Remote Similarity NPC154258
0.6438 Remote Similarity NPC470769
0.6393 Remote Similarity NPC26394
0.6308 Remote Similarity NPC253878
0.6308 Remote Similarity NPC471414
0.6267 Remote Similarity NPC470828
0.6119 Remote Similarity NPC163898
0.5949 Remote Similarity NPC470827
0.5797 Remote Similarity NPC480707
0.5714 Remote Similarity NPC300757
0.5672 Remote Similarity NPC264706
0.5606 Remote Similarity NPC472961
0.5606 Remote Similarity NPC472962
0.5541 Remote Similarity NPC469889
0.5526 Remote Similarity NPC260397
0.5455 Remote Similarity NPC177160
0.5312 Remote Similarity NPC187616
0.5312 Remote Similarity NPC193026
0.5312 Remote Similarity NPC49603
0.5303 Remote Similarity NPC193722
0.5303 Remote Similarity NPC83375
0.5263 Remote Similarity NPC236166
0.5231 Remote Similarity NPC479109
0.5224 Remote Similarity NPC29799
0.5224 Remote Similarity NPC263367
0.5224 Remote Similarity NPC54743
0.52 Remote Similarity NPC180768
0.5094 Remote Similarity NPC271985

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473408 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