Natural Product: NPC477239

Natural Product IDNPC477239
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 4,6,12-Trihydroxy-8,16-bis(4-hydroxyphenyl)-15-oxatetracyclo[8.6.1.02,7.014,17]heptadeca-1(16),2(7),3,5,10(17),11,13-heptaen-9-one
IUPAC Name 4,6,12-trihydroxy-8,16-bis(4-hydroxyphenyl)-15-oxatetracyclo[8.6.1.02,7.014,17]heptadeca-1(16),2(7),3,5,10(17),11,13-heptaen-9-one
Synonyms Shoreaphenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 10844302
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 HMIFNEKPRFKIQX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C28H18O7/c29-15-5-1-13(2-6-15)23-24-19(9-17(31)11-21(24)33)26-25-20(27(23)34)10-18(32)12-22(25)35-28(26)14-3-7-16(30)8-4-14/h1-12,23,29-33H
SMILES C1=CC(=CC=C1C2C3=C(C=C(C=C3O)O)C4=C(OC5=CC(=CC(=C54)C2=O)O)C6=CC=C(C=C6)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   466.11 Volume:   466.126
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Van der Waals volume.
Dense:   1.0 LogP:   4.301
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.694
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.389
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The logarithm of aqueous solubility value.
Rotatable Bonds:   2.0 Rigid Bonds:   33.0
TPSA:   131.36
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   6.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.228 GASA:   1.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.406 Fsp3:   0.036
MCE-18:   104.345
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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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.998 Fluc inhibitor:   0.658
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.761
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.809
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.607 Promiscuous compounds:   0.034

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.205 MDCK Permeability:   -4.717
Pgp-inhibitor:   0.001 Pgp-substrate:   0.668
PAMPA:   0.746
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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):   0.0
20% Bioavailability (F20%):   0.171 30% Bioavailability (F30%):   0.896
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.926
Plasma Protein Binding (PPB):   93.615% Volume Distribution (VD):   -0.112
Fu: 11.507%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.965
OATP1B3 inhibitor:   0.985 BCRP inhibitor:   0.271
BSEP inhibitor:   0.931

ADMET: Metabolism

CYP1A2-inhibitor:   0.012 CYP1A2-substrate:   0.036
CYP2C19-inhibitor:   0.031 CYP2C19-substrate:   0.019
CYP2C9-inhibitor:   0.116 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.211 CYP2D6-substrate:   0.998
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.202
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.997
HLM stability:   0.364
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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):  3.169 Half-life (T1/2):  2.28

ADMET: Toxicity

hERG Blockers:  0.149 hERG Blockers (10um):  0.675
Human Hepatotoxicity (H-HT):  0.525 Drug-induced Liver Injury (DILI):  0.507
AMES Toxicity:  0.449 Rat Oral Acute Toxicity:  0.563
Maximum Recommended Daily Dose:  0.958 Skin Sensitization:  0.844
Carcinogencity:  0.695 Eye Corrosion:  0.003
Eye Irritation:  0.973 Respiratory Toxicity:  0.788
Drug-induced Neurotoxicity:  0.051 Ototoxicity:  0.187
Hematotoxicity:  0.019 Drug-induced Nephrotoxicity:  0.013
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.05
A549 Cytotoxicity:  0.685 Hek293 Cytotoxicity:  0.97
BCF:   1.156
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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:   4.36
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.746
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.625
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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
NPO14000 Hopea exalata Species Dipterocarpaceae Eukaryota stem bark Botanical Garden at Jianfeng Town, Ledong County, Hainan Province, China 2004-JUL PMID[17190464]
NPO14000 Hopea exalata Species Dipterocarpaceae 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
NPT4885 Individual protein Urease Canavalia ensiformis IC50 = 126800 nM PMID[17190464]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT826 Organism Magnaporthe oryzae Magnaporthe oryzae MIC = 27.3 ug/ml PMID[17190464]
NPT962 Organism Alternaria alternata Alternaria alternata MIC = 50 ug/ml PMID[17190464]
NPT2648 Organism Fusarium oxysporum f. sp. vasinfectum Fusarium oxysporum f. sp. vasinfectum MIC > 50 ug/ml PMID[17190464]
NPT1199 Organism Valsa mali Valsa mali MIC = 7.13 ug/ml PMID[17190464]
NPT2705 Organism Alternaria solani Alternaria solani MIC > 50 ug/ml PMID[17190464]
NPT2637 Organism Colletotrichum lagenarium Colletotrichum lagenarium MIC > 50 ug/ml PMID[17190464]

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 NPC477239 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 NPC3448
0.6944 Remote Similarity NPC474591
0.5854 Remote Similarity NPC486487
0.506 Remote Similarity NPC475783

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC477239 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