Natural Product: NPC191835

Natural Product IDNPC191835
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Zearalanone
IUPAC Name (11S)-15,17-dihydroxy-11-methyl-12-oxabicyclo[12.4.0]octadeca-1(18),14,16-triene-7,13-dione
Synonyms Alpha-Zearalenol; Zearalanone
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL491499
PubChem CID 108003
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 APJDQUGPCJRQRJ-LBPRGKRZSA-N
Standard InCHI InChI=1S/C18H24O5/c1-12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h10-12,20-21H,2-9H2,1H3/t12-/m0/s1
SMILES C[C@H]1CCCC(=O)CCCCCc2cc(cc(c2C(=O)O1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   320.16 Volume:   333.54
?
Van der Waals volume.
Dense:   0.96 LogP:   2.43
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.571
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.826
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   21.0
TPSA:   83.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   5.0
H-Bond Donor:   2.0 Rings:   2.0
Heavy Atoms:   5.0

MedChem Properties

QED Drug-Likeness Score:   0.715 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.426 Fsp3:   0.556
MCE-18:   47.357
?
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:   0.035 Fluc inhibitor:   0.336
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.181
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.226
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.413 Promiscuous compounds:   0.213

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.759 MDCK Permeability:   -4.727
Pgp-inhibitor:   0.83 Pgp-substrate:   0.001
PAMPA:   0.012
?
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%):   0.004 30% Bioavailability (F30%):   0.307
50% Bioavailability (F50%):   0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.05 MRP1:   0.907
Plasma Protein Binding (PPB):   86.785% Volume Distribution (VD):   0.211
Fu: 13.448%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.439
BSEP inhibitor:   0.995

ADMET: Metabolism

CYP1A2-inhibitor:   0.978 CYP1A2-substrate:   0.141
CYP2C19-inhibitor:   0.028 CYP2C19-substrate:   0.007
CYP2C9-inhibitor:   0.999 CYP2C9-substrate:   0.014
CYP2D6-inhibitor:   0.671 CYP2D6-substrate:   0.863
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.434
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.849
HLM stability:   0.997
?
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):  3.941 Half-life (T1/2):  0.972

ADMET: Toxicity

hERG Blockers:  0.032 hERG Blockers (10um):  0.305
Human Hepatotoxicity (H-HT):  0.418 Drug-induced Liver Injury (DILI):  0.429
AMES Toxicity:  0.475 Rat Oral Acute Toxicity:  0.101
Maximum Recommended Daily Dose:  0.779 Skin Sensitization:  0.981
Carcinogencity:  0.368 Eye Corrosion:  0.709
Eye Irritation:  0.995 Respiratory Toxicity:  0.468
Drug-induced Neurotoxicity:  0.233 Ototoxicity:  0.161
Hematotoxicity:  0.113 Drug-induced Nephrotoxicity:  0.416
Genotoxicity:  0.054 RPMI-8226 Immunitoxicity:  0.086
A549 Cytotoxicity:  0.57 Hek293 Cytotoxicity:  0.516
BCF:   0.606
?
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:   3.201
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.37
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.833
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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
NPO27821.1 Pochonia chlamydosporia Under-species n.a. n.a. n.a. n.a. n.a. PMID[12828470]
NPO22748 Neophaeosphaeria quadriseptata Species Leptosphaeriaceae Eukaryota n.a. n.a. n.a. PMID[16499313]
NPO40515 Chaetomium chiversii Species Chaetomiaceae Eukaryota n.a. n.a. n.a. PMID[16499313]
NPO22748 Neophaeosphaeria quadriseptata Species Leptosphaeriaceae 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
NPT299 Individual protein Androgen Receptor Rattus norvegicus IC50 = 42657.95 nM PMID[17190457]
NPT299 Individual protein Androgen Receptor Rattus norvegicus IC50 = 10000.0 nM PMID[10425119]
NPT248 Individual protein Estrogen receptor beta Homo sapiens EC50 = 38.0 nM DOI[10.6019/CHEMBL1201861]
NPT248 Individual protein Estrogen receptor beta Homo sapiens EC50 = 660.0 nM DOI[10.6019/CHEMBL1201861]
NPT1429 Individual protein Heat shock protein HSP 90-beta Homo sapiens IC50 = 90.0 nM PMID[19734910]
NPT198 Individual protein Vitamin D receptor Homo sapiens Potency n.a. 100000.0 nM PMID[20086162]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 25929.0 nM PMID[24645629]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 4610.9 nM PMID[19203247]
NPT10 Individual protein Geminin Homo sapiens Potency n.a. 16360.1 nM PMID[19506058]
NPT483 Individual protein Prelamin-A/C Homo sapiens Potency = 28183.8 nM PMID[15730254]
NPT531 Individual protein Nuclear receptor ROR-gamma Mus musculus Potency = 35481.3 nM PMID[12193011]
NPT94 Individual protein Aldehyde dehydrogenase 1A1 Homo sapiens Potency = 44668.4 nM PMID[25435149]
NPT791 Individual protein Cruzipain Trypanosoma cruzi Potency = 28183.8 nM PMID[17908946]
NPT93 Individual protein Survival motor neuron protein Homo sapiens Potency = 3162.3 nM PMID[23811085]
NPT861 Individual protein Isocitrate dehydrogenase [NADP] cytoplasmic Homo sapiens Potency n.a. 29092.9 nM PMID[8450319]
NPT920 Individual protein Alpha-synuclein Homo sapiens Potency n.a. 15848.9 nM DrugMatrix in vitro pharmacology data
NPT535 Individual protein Parathyroid hormone receptor Homo sapiens Potency n.a. 50118.7 nM PMID[24056020]
NPT2264 Protein family Heat shock protein HSP90 Homo sapiens IC50 = 2197.6 nM PMID[18054490]
NPT2264 Protein family Heat shock protein HSP90 Homo sapiens IC50 > 30000.0 nM PMID[3210015]
NPT64 Individual protein ATPase family AAA domain-containing protein 5 Homo sapiens Potency n.a. 20596.2 nM PMID[16933872]

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 > 25000.0 nM PMID[15787444]
NPT397 Cell line NCI-H460 Homo sapiens IC50 > 25000.0 nM PMID[24950030]
NPT395 Cell line SF-268 Homo sapiens IC50 > 50000.0 nM PMID[24950030]
NPT71 Cell line HEK293 Homo sapiens Potency n.a. 25929.0 nM PMID[22194678]
NPT189 Cell line Vero Chlorocebus aethiops IC50 = 151260.0 nM PMID[19654408]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 9285.0 nM PMID[19654408]
NPT6 Organism Plasmodium falciparum Plasmodium falciparum Potency n.a. 4147.5 nM PMID[21652215]
NPT2254 Organism Schistosoma mansoni Schistosoma mansoni In vitro activity n.a. n.a. n.a. Using ChEMBL to complement schistosome drug discovery
NPT2 Others Unspecified n.a. Potency = 18356.4 nM PMID[3437287]
NPT2 Others Unspecified n.a. Potency n.a. 8912.5 nM PMID[25651042]
NPT2 Others Unspecified n.a. Potency n.a. 11220.2 nM PMID[16933872]
NPT2 Others Unspecified n.a. Potency n.a. 20596.2 nM Open TG-GATES in vivo data: Hematology
NPT2 Others Unspecified n.a. Potency n.a. 22387.2 nM PMID[19687244]

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 NPC191835 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
0.82 Intermediate Similarity NPC70380
0.7455 Intermediate Similarity NPC610163
0.7321 Intermediate Similarity NPC212693
0.7321 Intermediate Similarity NPC94248
0.6379 Remote Similarity NPC608268
0.6066 Remote Similarity NPC33144
0.6034 Remote Similarity NPC105456
0.6034 Remote Similarity NPC139634
0.6 Remote Similarity NPC609527
0.6 Remote Similarity NPC611086
0.5806 Remote Similarity NPC472035
0.5714 Remote Similarity NPC481134
0.5469 Remote Similarity NPC472006
0.5439 Remote Similarity NPC609111
0.5323 Remote Similarity NPC53649
0.5312 Remote Similarity NPC609495
0.5283 Remote Similarity NPC219892
0.5283 Remote Similarity NPC235115
0.5161 Remote Similarity NPC1704
0.5161 Remote Similarity NPC67650
0.5152 Remote Similarity NPC610162

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC191835 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