Natural Product: NPC74413

Natural Product IDNPC74413
Common Name
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The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Asterriquinone D
IUPAC Name 2,5-bis(1H-indol-3-yl)-3,6-dimethoxycyclohexa-2,5-diene-1,4-dione
Synonyms Asterriquinone D
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL512621
PubChem CID 23247888
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000002] Organoheterocyclic compounds
      • [CHEMONTID:0000211] Indoles and derivatives
        • [CHEMONTID:0002497] Indoles

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 IVPGMNQTDHNSBX-UHFFFAOYSA-N
Standard InCHI InChI=1S/C24H18N2O4/c1-29-23-19(15-11-25-17-9-5-3-7-13(15)17)22(28)24(30-2)20(21(23)27)16-12-26-18-10-6-4-8-14(16)18/h3-12,25-26H,1-2H3
SMILES COC1=C(c2c[nH]c3ccccc23)C(=O)C(=C(c2c[nH]c3ccccc23)C1=O)OC

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   398.13 Volume:   406.395
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Van der Waals volume.
Dense:   0.98 LogP:   2.746
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.367
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.499
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The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   28.0
TPSA:   84.18
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Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   2.0 Rings:   5.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.504 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.708 Fsp3:   0.083
MCE-18:   54.0
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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:   1
Colloidal aggregators:   0.987 Fluc inhibitor:   0.416
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.25
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.774
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.239 Promiscuous compounds:   0.947

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.8 MDCK Permeability:   -4.708
Pgp-inhibitor:   0.924 Pgp-substrate:   0.001
PAMPA:   0.351
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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):   0.413
20% Bioavailability (F20%):   0.016 30% Bioavailability (F30%):   0.743
50% Bioavailability (F50%):   0.945

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.009 MRP1:   0.17
Plasma Protein Binding (PPB):   97.85% Volume Distribution (VD):   0.039
Fu: 1.972%
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The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.991
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.006
BSEP inhibitor:   0.993

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   1.0
CYP2C9-inhibitor:   0.869 CYP2C9-substrate:   0.839
CYP2D6-inhibitor:   0.842 CYP2D6-substrate:   1.0
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
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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):  0.983 Half-life (T1/2):  1.381

ADMET: Toxicity

hERG Blockers:  0.141 hERG Blockers (10um):  0.392
Human Hepatotoxicity (H-HT):  0.857 Drug-induced Liver Injury (DILI):  0.948
AMES Toxicity:  0.878 Rat Oral Acute Toxicity:  0.421
Maximum Recommended Daily Dose:  0.762 Skin Sensitization:  0.465
Carcinogencity:  0.825 Eye Corrosion:  0.0
Eye Irritation:  0.462 Respiratory Toxicity:  0.29
Drug-induced Neurotoxicity:  0.771 Ototoxicity:  0.526
Hematotoxicity:  0.83 Drug-induced Nephrotoxicity:  0.808
Genotoxicity:  0.982 RPMI-8226 Immunitoxicity:  0.213
A549 Cytotoxicity:  0.177 Hek293 Cytotoxicity:  0.403
BCF:   1.536
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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:   4.452
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   5.676
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.631
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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
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. from the rhizosphere of Opuntia versicolor of the Sonoran Desert n.a. PMID[14695798]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[16124769]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[18271552]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[22360613]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[24534845]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[25671343]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[2921224]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[30207465]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[32163285]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[32897070]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[8984154]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2595 Aspergillus terreus Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2595 Aspergillus terreus Species Aspergillaceae 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
NPT397 Cell line NCI-H460 Homo sapiens IC50 = 19900.0 nM PMID[14695799]
NPT83 Cell line MCF7 Homo sapiens IC50 = 17700.0 nM DrugMatrix in vitro pharmacology data
NPT395 Cell line SF-268 Homo sapiens IC50 = 15800.0 nM PMID[17663585]

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 NPC74413 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
0.7018 Intermediate Similarity NPC260900
0.6316 Remote Similarity NPC474412
0.6042 Remote Similarity NPC67288
0.5918 Remote Similarity NPC603879
0.5556 Remote Similarity NPC300149
0.5532 Remote Similarity NPC138370
0.5273 Remote Similarity NPC131887
0.5217 Remote Similarity NPC42372
0.5139 Remote Similarity NPC604623
0.5102 Remote Similarity NPC72435
0.5098 Remote Similarity NPC310665
0.5094 Remote Similarity NPC602656

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC74413 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