Natural Product: NPC215711

Natural Product IDNPC215711
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (5E)-7-Oxozeaenol
IUPAC Name (2E,5S,6S,8E,11S)-5,6,15-trihydroxy-17-methoxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(18),2,8,14,16-pentaene-7,13-dione
Synonyms (5E)-7-Oxozeaenol
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1801950
PubChem CID 9799061
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000147] Macrolides and analogues
        • [CHEMONTID:0001788] Zearalenones

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 NEQZWEXWOFPKOT-ULSULSEOSA-N
Standard InCHI InChI=1S/C19H22O7/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/h3-4,6-7,9-11,15,18,21-23H,5,8H2,1-2H3/b6-4+,7-3+/t11-,15-,18+/m0/s1
SMILES C[C@H]1C/C=C/C(=O)[C@H]([C@H](C/C=C/c2cc(cc(c2C(=O)O1)O)OC)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   362.14 Volume:   363.144
?
Van der Waals volume.
Dense:   0.997 LogP:   1.561
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.859
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.466
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The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   21.0
TPSA:   113.29
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Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   3.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.65 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.354 Fsp3:   0.368
MCE-18:   50.769
?
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:   0.606 Fluc inhibitor:   0.781
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.197
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.417
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.39 Promiscuous compounds:   0.775

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.211 MDCK Permeability:   -4.812
Pgp-inhibitor:   0.362 Pgp-substrate:   0.261
PAMPA:   0.365
?
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):   0.082
20% Bioavailability (F20%):   0.154 30% Bioavailability (F30%):   0.935
50% Bioavailability (F50%):   0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.268
Plasma Protein Binding (PPB):   84.607% Volume Distribution (VD):   0.079
Fu: 13.13%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.997
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.768
BSEP inhibitor:   0.946

ADMET: Metabolism

CYP1A2-inhibitor:   0.041 CYP1A2-substrate:   0.039
CYP2C19-inhibitor:   0.002 CYP2C19-substrate:   0.044
CYP2C9-inhibitor:   0.019 CYP2C9-substrate:   0.242
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.134
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.999
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.968
?
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):  4.23 Half-life (T1/2):  1.341

ADMET: Toxicity

hERG Blockers:  0.064 hERG Blockers (10um):  0.103
Human Hepatotoxicity (H-HT):  0.976 Drug-induced Liver Injury (DILI):  0.997
AMES Toxicity:  0.919 Rat Oral Acute Toxicity:  0.082
Maximum Recommended Daily Dose:  0.99 Skin Sensitization:  1.0
Carcinogencity:  0.642 Eye Corrosion:  0.0
Eye Irritation:  0.882 Respiratory Toxicity:  0.951
Drug-induced Neurotoxicity:  0.974 Ototoxicity:  0.25
Hematotoxicity:  0.075 Drug-induced Nephrotoxicity:  0.993
Genotoxicity:  1.0 RPMI-8226 Immunitoxicity:  0.741
A549 Cytotoxicity:  0.986 Hek293 Cytotoxicity:  0.962
BCF:   0.988
?
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:   3.614
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.897
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.339
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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
NPT3442 Individual protein Mitogen-activated protein kinase kinase kinase 7 Homo sapiens IC50 = 1300.0 nM PMID[26481152]
NPT721 Individual protein Nuclear factor NF-kappa-B p65 subunit Homo sapiens IC50 = 11500.0 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 = 4900.0 nM PMID[21513293]
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 1200.0 nM PMID[21513293]
NPT395 Cell line SF-268 Homo sapiens IC50 = 5600.0 nM PMID[21513293]
NPT139 Cell line HT-29 Homo sapiens IC50 = 4400.0 nM PMID[21513293]
NPT400 Cell line MDA-MB-435 Homo sapiens IC50 = 5500.0 nM PMID[21513293]
NPT30114 Cell line Splenocyte Mus musculus IC50 = 6200.0 nM PMID[33544615]
NPT30114 Cell line Splenocyte Mus musculus IC50 = 6000.0 nM PMID[33544615]
NPT30114 Cell line Splenocyte Mus musculus Activity n.a. n.a. n.a. PMID[33544615]
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 NPC215711 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 NPC73411
1.0 High Similarity NPC600572
1.0 High Similarity NPC609200
1.0 High Similarity NPC610004
0.7576 Intermediate Similarity NPC86373
0.7576 Intermediate Similarity NPC277426
0.7424 Intermediate Similarity NPC602143
0.7313 Intermediate Similarity NPC210320
0.7313 Intermediate Similarity NPC600729
0.7313 Intermediate Similarity NPC608895
0.7313 Intermediate Similarity NPC610003
0.6667 Remote Similarity NPC210425
0.6667 Remote Similarity NPC280404
0.6667 Remote Similarity NPC601973
0.662 Remote Similarity NPC99381
0.6571 Remote Similarity NPC602776
0.6429 Remote Similarity NPC603435
0.6143 Remote Similarity NPC603637
0.6 Remote Similarity NPC474385
0.589 Remote Similarity NPC599920
0.589 Remote Similarity NPC607216
0.589 Remote Similarity NPC611286
0.5128 Remote Similarity NPC469670
0.5128 Remote Similarity NPC469619

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC215711 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