Natural Product: NPC96342

Natural Product IDNPC96342
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Stemofuran E
IUPAC Name 2-(3-hydroxy-5-methoxy-2,4-dimethylphenyl)-1-benzofuran-4-ol
Synonyms Stemofuran L
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL449756
PubChem CID 641367
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 LWQZXNMQJHPTQF-UHFFFAOYSA-N
Standard InCHI InChI=1S/C17H16O4/c1-9-11(7-15(20-3)10(2)17(9)19)16-8-12-13(18)5-4-6-14(12)21-16/h4-8,18-19H,1-3H3
SMILES COc1cc(c2oc3c(c2)c(O)ccc3)c(c(c1C)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   284.1 Volume:   293.625
?
Van der Waals volume.
Dense:   0.968 LogP:   3.434
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.061
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.188
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   16.0
TPSA:   62.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   3.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.742 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.461 Fsp3:   0.176
MCE-18:   18.0
?
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:   0.724 Fluc inhibitor:   0.829
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.936
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.631
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.429 Promiscuous compounds:   0.252

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.969 MDCK Permeability:   -4.734
Pgp-inhibitor:   0.495 Pgp-substrate:   0.19
PAMPA:   0.315
?
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):   0.07
20% Bioavailability (F20%):   0.348 30% Bioavailability (F30%):   0.321
50% Bioavailability (F50%):   0.873

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.154 MRP1:   0.822
Plasma Protein Binding (PPB):   95.692% Volume Distribution (VD):   -0.179
Fu: 4.429%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.966 BCRP inhibitor:   0.759
BSEP inhibitor:   0.914

ADMET: Metabolism

CYP1A2-inhibitor:   0.87 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.944 CYP2C19-substrate:   0.991
CYP2C9-inhibitor:   0.994 CYP2C9-substrate:   0.235
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.183
CYP3A4-inhibitor:   0.026 CYP3A4-substrate:   0.573
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   0.996
HLM stability:   0.938
?
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):  9.064 Half-life (T1/2):  0.845

ADMET: Toxicity

hERG Blockers:  0.058 hERG Blockers (10um):  0.469
Human Hepatotoxicity (H-HT):  0.449 Drug-induced Liver Injury (DILI):  0.605
AMES Toxicity:  0.54 Rat Oral Acute Toxicity:  0.52
Maximum Recommended Daily Dose:  0.426 Skin Sensitization:  0.634
Carcinogencity:  0.668 Eye Corrosion:  0.565
Eye Irritation:  0.993 Respiratory Toxicity:  0.87
Drug-induced Neurotoxicity:  0.159 Ototoxicity:  0.177
Hematotoxicity:  0.194 Drug-induced Nephrotoxicity:  0.115
Genotoxicity:  0.474 RPMI-8226 Immunitoxicity:  0.083
A549 Cytotoxicity:  0.262 Hek293 Cytotoxicity:  0.353
BCF:   1.107
?
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:   3.784
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.914
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.319
?
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
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota Leaves, rhizomes, and roots southeast Thailand near Chonburi 2000-Feb, 2001-Jan PMID[12088422]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15104502]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota slowly dried tubers Bangkok, Thailand n.a. PMID[15679323]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[15679323]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. Southeast Thailand near Chonburi, Khao Khieo, close to the Chanthathen waterfall and Sri Racha n.a. PMID[15679323]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots; Stems n.a. n.a. PMID[19374387]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Stems n.a. n.a. PMID[20415428]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. root n.a. PMID[21049906]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21049906]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota Roots Lampang Province, Thailand 2009-APR PMID[21126060]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. root n.a. PMID[21126060]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. rhizome n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. tuberous root n.a. PMID[21902195]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. PMID[21902195]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9624 Myoporum bontioides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO30254 Stemona collinsae Species Stemonaceae Eukaryota leaf and root n.a. n.a. Database[Title]
NPO9624 Myoporum bontioides Species Scrophulariaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13984 Helenium radiatum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10593 Aspergillus pulvinus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28187 Duguetia confinis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO221 Stemona aphylla Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO1235 Stemona curtisii Species Stemonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO866 Heliomeris longifolia Species Asteraceae 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
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana EC50 = 26.0 ug.mL-1 PMID[12088422]
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana EC90 > 200.0 ug ml-1 PMID[12088422]
NPT635 Organism Botryotinia fuckeliana Botryotinia fuckeliana MIC > 200.0 ug.mL-1 PMID[12088422]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 250.0 ug.mL-1 PMID[21049906]
NPT1228 Organism Streptococcus pyogenes Streptococcus pyogenes MIC = 250.0 ug.mL-1 PMID[21049906]
NPT20 Organism Candida albicans Candida albicans MIC = 250.0 ug.mL-1 PMID[21049906]
NPT173 Organism Klebsiella pneumoniae Klebsiella pneumoniae MIC = 62.5 ug.mL-1 PMID[21126060]
NPT20 Organism Candida albicans Candida albicans MIC = 31.3 ug.mL-1 PMID[21126060]
NPT3821 Organism Alternaria citri Alternaria citri EC50 = 5.0 ug.mL-1 PMID[12088422]
NPT3660 Organism Fusarium avenaceum Fusarium avenaceum EC50 = 18.0 ug.mL-1 PMID[12088422]
NPT1780 Organism Davidiella tassiana Davidiella tassiana EC50 = 0.8 ug.mL-1 PMID[12088422]
NPT3821 Organism Alternaria citri Alternaria citri EC90 > 200.0 ug ml-1 PMID[12088422]
NPT3660 Organism Fusarium avenaceum Fusarium avenaceum EC90 > 200.0 ug ml-1 PMID[12088422]
NPT1780 Organism Davidiella tassiana Davidiella tassiana EC90 > 200.0 ug ml-1 PMID[12088422]
NPT3821 Organism Alternaria citri Alternaria citri MIC > 200.0 ug.mL-1 PMID[12088422]
NPT3660 Organism Fusarium avenaceum Fusarium avenaceum MIC > 200.0 ug.mL-1 PMID[12088422]
NPT1780 Organism Davidiella tassiana Davidiella tassiana MIC > 200.0 ug.mL-1 PMID[12088422]
NPT19 Organism Escherichia coli Escherichia coli MIC = 250.0 ug.mL-1 PMID[21049906]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 250.0 ug.mL-1 PMID[21049906]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC = 250.0 ug.mL-1 PMID[21049906]
NPT19 Organism Escherichia coli Escherichia coli MIC = 62.5 ug.mL-1 PMID[21126060]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 62.5 ug.mL-1 PMID[21126060]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC = 15.6 ug.mL-1 PMID[21126060]
NPT85 Organism Filobasidiella neoformans Cryptococcus neoformans MIC = 7.8 ug.mL-1 PMID[21126060]

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 NPC96342 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
0.7407 Intermediate Similarity NPC246647
0.7407 Intermediate Similarity NPC115324
0.7407 Intermediate Similarity NPC212967
0.7037 Intermediate Similarity NPC164110
0.5862 Remote Similarity NPC98926
0.55 Remote Similarity NPC106372
0.5333 Remote Similarity NPC13282
0.5323 Remote Similarity NPC180924
0.5161 Remote Similarity NPC58668

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC96342 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