Natural Product: NPC86373

Natural Product IDNPC86373
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 7-Epi-Zeaenol
IUPAC Name (2E,5S,6S,7R,8E,11S)-5,6,7,15-tetrahydroxy-17-methoxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(14),2,8,15,17-pentaen-13-one
Synonyms 7-Epi-Zeaenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1801949
PubChem CID 53355130
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues

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 BPOLRDGTYHVUAY-OURSJTMWSA-N
Standard InCHI InChI=1S/C19H24O7/c1-11-5-3-7-14(20)18(23)15(21)8-4-6-12-9-13(25-2)10-16(22)17(12)19(24)26-11/h3-4,6-7,9-11,14-15,18,20-23H,5,8H2,1-2H3/b6-4+,7-3+/t11-,14+,15-,18+/m0/s1
SMILES COc1cc2/C=C/C[C@H](O)[C@H](O)[C@H](O)/C=C/C[C@@H](OC(=O)c2c(c1)O)C

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   364.15 Volume:   365.78
?
Van der Waals volume.
Dense:   0.996 LogP:   1.49
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.856
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.263
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   20.0
TPSA:   116.45
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   4.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.439 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.533 Fsp3:   0.421
MCE-18:   51.667
?
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:   0.364 Fluc inhibitor:   0.441
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.219
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.211
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.319 Promiscuous compounds:   0.71

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.269 MDCK Permeability:   -4.888
Pgp-inhibitor:   0.028 Pgp-substrate:   0.052
PAMPA:   0.263
?
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):   0.686
20% Bioavailability (F20%):   0.684 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.077
Plasma Protein Binding (PPB):   83.327% Volume Distribution (VD):   -0.055
Fu: 15.056%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.57
BSEP inhibitor:   0.411

ADMET: Metabolism

CYP1A2-inhibitor:   0.003 CYP1A2-substrate:   0.009
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.081
CYP2C9-inhibitor:   0.078 CYP2C9-substrate:   0.246
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.003
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.993
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.895
?
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):  5.139 Half-life (T1/2):  1.407

ADMET: Toxicity

hERG Blockers:  0.036 hERG Blockers (10um):  0.159
Human Hepatotoxicity (H-HT):  0.934 Drug-induced Liver Injury (DILI):  0.988
AMES Toxicity:  0.955 Rat Oral Acute Toxicity:  0.183
Maximum Recommended Daily Dose:  0.981 Skin Sensitization:  1.0
Carcinogencity:  0.743 Eye Corrosion:  0.001
Eye Irritation:  0.841 Respiratory Toxicity:  0.93
Drug-induced Neurotoxicity:  0.931 Ototoxicity:  0.41
Hematotoxicity:  0.108 Drug-induced Nephrotoxicity:  0.99
Genotoxicity:  0.999 RPMI-8226 Immunitoxicity:  0.604
A549 Cytotoxicity:  0.994 Hek293 Cytotoxicity:  0.853
BCF:   0.601
?
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:   3.223
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.549
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.945
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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
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota Radix n.a. n.a. PMID[29236488]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO4414 Lilium lancifolium Species Liliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO802 Halla parthenopeia n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO4414 Lilium lancifolium Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15156 Euphorbia tithymaloides Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4414 Lilium lancifolium Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO4414 Lilium lancifolium Species Liliaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO4414 Lilium lancifolium Species Liliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO25209 Curcuma aromatica Species Zingiberaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15156 Euphorbia tithymaloides Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO802 Halla parthenopeia n.a. n.a. n.a. 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
NPT721 Individual protein Nuclear factor NF-kappa-B p65 subunit Homo sapiens IC50 > 50000.0 nM PMID[21513293]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT83 Cell line MCF7 Homo sapiens IC50 > 100000.0 nM PMID[21513293]
NPT397 Cell line NCI-H460 Homo sapiens IC50 > 100000.0 nM PMID[21513293]
NPT395 Cell line SF-268 Homo sapiens IC50 > 100000.0 nM PMID[21513293]
NPT139 Cell line HT-29 Homo sapiens IC50 > 25000.0 nM PMID[21513293]
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 > 25000.0 nM PMID[21513293]
NPT602 Organism Mycobacterium smegmatis Mycobacterium smegmatis MIC > 500.0 ug.mL-1 PMID[21513293]
NPT79 Organism Bacillus subtilis Bacillus subtilis MIC > 500.0 ug.mL-1 PMID[21513293]
NPT19 Organism Escherichia coli Escherichia coli MIC > 500.0 ug.mL-1 PMID[21513293]
NPT16 Organism Staphylococcus aureus Staphylococcus aureus MIC > 500.0 ug.mL-1 PMID[21513293]

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 NPC86373 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 NPC277426
0.7576 Intermediate Similarity NPC73411
0.7576 Intermediate Similarity NPC215711
0.7576 Intermediate Similarity NPC600572
0.7576 Intermediate Similarity NPC609200
0.7576 Intermediate Similarity NPC610004
0.7164 Intermediate Similarity NPC210425
0.7164 Intermediate Similarity NPC280404
0.7164 Intermediate Similarity NPC601973
0.6667 Remote Similarity NPC602143
0.662 Remote Similarity NPC469670
0.662 Remote Similarity NPC469619
0.6571 Remote Similarity NPC210320
0.6571 Remote Similarity NPC600729
0.6571 Remote Similarity NPC608895
0.6571 Remote Similarity NPC610003
0.6197 Remote Similarity NPC603435
0.6143 Remote Similarity NPC603637
0.6 Remote Similarity NPC474385
0.5753 Remote Similarity NPC70016
0.5676 Remote Similarity NPC599920
0.5676 Remote Similarity NPC607216
0.5676 Remote Similarity NPC611286
0.5571 Remote Similarity NPC158472
0.5333 Remote Similarity NPC215921
0.5128 Remote Similarity NPC99381
0.5065 Remote Similarity NPC602776

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC86373 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