Natural Product: NPC476185

Natural Product IDNPC476185
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4-Hydroxy-7-(4-Hydroxyphenyl)-2,3,3-Trimethyl-2H-Furo[3,2-G]Chromen-5-One
IUPAC Name 4-hydroxy-7-(4-hydroxyphenyl)-2,3,3-trimethyl-2H-furo[3,2-g]chromen-5-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL551658
PubChem CID 45270713
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001759] Furanoflavones

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 YPVUORZILHLSOT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H18O5/c1-10-20(2,3)18-16(24-10)9-15-17(19(18)23)13(22)8-14(25-15)11-4-6-12(21)7-5-11/h4-10,21,23H,1-3H3
SMILES CC1C(C2=C(O1)C=C3C(=C2O)C(=O)C=C(O3)C4=CC=C(C=C4)O)(C)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   338.12 Volume:   343.11
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Van der Waals volume.
Dense:   0.985 LogP:   3.304
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.697
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.703
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   22.0
TPSA:   79.9
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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:   0.703 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.291 Fsp3:   0.25
MCE-18:   79.0
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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:   Rejected GSK Rule:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.499 Fluc inhibitor:   0.693
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.909
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.687
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.319 Promiscuous compounds:   0.238

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.893 MDCK Permeability:   -4.748
Pgp-inhibitor:   0.783 Pgp-substrate:   0.121
PAMPA:   0.244
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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%):   0.404 30% Bioavailability (F30%):   0.61
50% Bioavailability (F50%):   0.986

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.039 MRP1:   0.992
Plasma Protein Binding (PPB):   97.861% Volume Distribution (VD):   -0.226
Fu: 1.801%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.973
OATP1B3 inhibitor:   0.984 BCRP inhibitor:   0.733
BSEP inhibitor:   0.998

ADMET: Metabolism

CYP1A2-inhibitor:   0.021 CYP1A2-substrate:   0.559
CYP2C19-inhibitor:   0.009 CYP2C19-substrate:   0.23
CYP2C9-inhibitor:   0.976 CYP2C9-substrate:   0.016
CYP2D6-inhibitor:   0.578 CYP2D6-substrate:   0.991
CYP3A4-inhibitor:   0.49 CYP3A4-substrate:   0.563
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.418
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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):  5.463 Half-life (T1/2):  1.019

ADMET: Toxicity

hERG Blockers:  0.096 hERG Blockers (10um):  0.52
Human Hepatotoxicity (H-HT):  0.399 Drug-induced Liver Injury (DILI):  0.673
AMES Toxicity:  0.483 Rat Oral Acute Toxicity:  0.603
Maximum Recommended Daily Dose:  0.874 Skin Sensitization:  0.692
Carcinogencity:  0.763 Eye Corrosion:  0.172
Eye Irritation:  0.992 Respiratory Toxicity:  0.839
Drug-induced Neurotoxicity:  0.126 Ototoxicity:  0.12
Hematotoxicity:  0.098 Drug-induced Nephrotoxicity:  0.086
Genotoxicity:  0.952 RPMI-8226 Immunitoxicity:  0.055
A549 Cytotoxicity:  0.311 Hek293 Cytotoxicity:  0.802
BCF:   1.58
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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:   4.446
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.575
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.114
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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
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae Eukaryota rhizomes n.a. n.a. PMID[19583252]
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae Eukaryota Rhizomes n.a. n.a. PMID[28169537]
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO11959 Helminthostachys zeylanica Species Ophioglossaceae 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
NPT65 Cell line HepG2 Homo sapiens IC50 > 10000.0 nM PMID[20797868]
NPT83 Cell line MCF7 Homo sapiens IC50 > 10000.0 nM PMID[20797868]

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 NPC476185 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
0.8475 Intermediate Similarity NPC476283
0.6833 Remote Similarity NPC78913
0.6269 Remote Similarity NPC265932
0.5873 Remote Similarity NPC120163
0.5625 Remote Similarity NPC18260
0.5625 Remote Similarity NPC198826
0.5625 Remote Similarity NPC234133
0.5455 Remote Similarity NPC478511
0.5385 Remote Similarity NPC10807
0.5385 Remote Similarity NPC161881
0.5231 Remote Similarity NPC241498
0.5217 Remote Similarity NPC284220
0.5211 Remote Similarity NPC110969
0.5079 Remote Similarity NPC130230
0.5075 Remote Similarity NPC159275
0.507 Remote Similarity NPC486096
0.507 Remote Similarity NPC205265

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC476185 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