Natural Product: NPC473739

Natural Product IDNPC473739
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Vesticarpan
IUPAC Name 9-methoxy-6a,11a-dihydro-6H-[1]benzofuro[3,2-c]chromene-3,4-diol
Synonyms vesticarpan
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL450694
PubChem CID 11536537
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0002506] Isoflavonoids
        • [CHEMONTID:0002617] Furanoisoflavonoids
          • [CHEMONTID:0001608] Pterocarpans

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 YRFDJOAWSXSLMG-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H14O5/c1-19-8-2-3-9-11-7-20-16-10(4-5-12(17)14(16)18)15(11)21-13(9)6-8/h2-6,11,15,17-18H,7H2,1H3
SMILES COC1=CC2=C(C=C1)C3COC4=C(C3O2)C=CC(=C4O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   286.08 Volume:   279.199
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Van der Waals volume.
Dense:   1.025 LogP:   2.389
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.627
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.464
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   68.15
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Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   4.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.789 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.355 Fsp3:   0.25
MCE-18:   69.3
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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:   1
Colloidal aggregators:   0.507 Fluc inhibitor:   0.804
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.068
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.288
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.561 Promiscuous compounds:   0.488

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.03 MDCK Permeability:   -4.771
Pgp-inhibitor:   0.017 Pgp-substrate:   0.01
PAMPA:   0.049
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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):   0.057
20% Bioavailability (F20%):   0.8 30% Bioavailability (F30%):   0.374
50% Bioavailability (F50%):   0.981

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.417 MRP1:   0.855
Plasma Protein Binding (PPB):   89.055% Volume Distribution (VD):   -0.468
Fu: 11.094%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.977
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.717
BSEP inhibitor:   0.632

ADMET: Metabolism

CYP1A2-inhibitor:   0.943 CYP1A2-substrate:   0.547
CYP2C19-inhibitor:   0.766 CYP2C19-substrate:   0.118
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.009
CYP2D6-inhibitor:   1.0 CYP2D6-substrate:   0.952
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.684
CYP2B6-substrate:   0.124 CYP2C8-inhibitor:   0.014
HLM stability:   0.924
?
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):  11.241 Half-life (T1/2):  1.96

ADMET: Toxicity

hERG Blockers:  0.173 hERG Blockers (10um):  0.675
Human Hepatotoxicity (H-HT):  0.476 Drug-induced Liver Injury (DILI):  0.624
AMES Toxicity:  0.624 Rat Oral Acute Toxicity:  0.395
Maximum Recommended Daily Dose:  0.405 Skin Sensitization:  0.572
Carcinogencity:  0.627 Eye Corrosion:  0.1
Eye Irritation:  0.968 Respiratory Toxicity:  0.716
Drug-induced Neurotoxicity:  0.203 Ototoxicity:  0.612
Hematotoxicity:  0.187 Drug-induced Nephrotoxicity:  0.237
Genotoxicity:  0.235 RPMI-8226 Immunitoxicity:  0.037
A549 Cytotoxicity:  0.373 Hek293 Cytotoxicity:  0.379
BCF:   1.341
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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:   3.83
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.459
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.698
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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
NPO24543 Platymiscium floribundum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[15787450]
NPO24543 Platymiscium floribundum Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[21866899]
NPO24543 Platymiscium floribundum Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO24543 Platymiscium floribundum Species Fabaceae 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
NPT404 Cell line CCRF-CEM Homo sapiens IC50 = 7.3 ug.mL-1 PMID[17503850]
NPT116 Cell line HL-60 Homo sapiens IC50 = 6.9 ug.mL-1 PubChem BioAssay data set
NPT180 Cell line HCT-8 Homo sapiens IC50 = 12.4 ug.mL-1 DOI[10.1007/s00044-011-9952-2]
NPT83 Cell line MCF7 Homo sapiens IC50 = 10.0 ug.mL-1 DOI[10.1007/s00044-011-9952-2]
NPT319 Cell line B16 Mus musculus IC50 = 2.7 ug.mL-1 PubChem BioAssay data set

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 NPC473739 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
1.0 High Similarity NPC232164
0.7736 Intermediate Similarity NPC309124
0.7091 Intermediate Similarity NPC184797
0.7091 Intermediate Similarity NPC39064
0.7091 Intermediate Similarity NPC47283
0.6667 Remote Similarity NPC294156
0.6667 Remote Similarity NPC256015
0.6441 Remote Similarity NPC605383
0.6207 Remote Similarity NPC32633
0.6182 Remote Similarity NPC474478
0.6182 Remote Similarity NPC606219
0.6 Remote Similarity NPC17343
0.5385 Remote Similarity NPC71288
0.5385 Remote Similarity NPC301961
0.5323 Remote Similarity NPC236306
0.5246 Remote Similarity NPC27495
0.5143 Remote Similarity NPC108674
0.5088 Remote Similarity NPC471215
0.5088 Remote Similarity NPC262573
0.5079 Remote Similarity NPC300798
0.5079 Remote Similarity NPC58137

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC473739 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