Natural Product: NPC227741

Natural Product IDNPC227741
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Auroglaucin
IUPAC Name 2-[(1E,3E,5E)-hepta-1,3,5-trienyl]-3,6-dihydroxy-5-(3-methylbut-2-enyl)benzaldehyde
Synonyms Auroglaucin
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1813666
PubChem CID 6434324
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001534] Quinone and hydroquinone lipids
          • [CHEMONTID:0002801] Prenylated hydroquinones

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 ZKBCBIRBLMTSPC-ZAJAATJQSA-N
Standard InCHI InChI=1S/C19H22O3/c1-4-5-6-7-8-9-16-17(13-20)19(22)15(12-18(16)21)11-10-14(2)3/h4-10,12-13,21-22H,11H2,1-3H3/b5-4+,7-6+,9-8+
SMILES C/C=C/C=C/C=C/c1c(C=O)c(c(CC=C(C)C)cc1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   298.16 Volume:   333.903
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Van der Waals volume.
Dense:   0.893 LogP:   4.112
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.534
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -5.339
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The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   11.0
TPSA:   57.53
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Topological Polar Surface Area.
 H-Bond Acceptor:   3.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   3.0

MedChem Properties

QED Drug-Likeness Score:   0.35 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.4 Fsp3:   0.211
MCE-18:   9.0
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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:   Accepted GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.949 Fluc inhibitor:   0.662
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.646
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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:   0.79 Promiscuous compounds:   0.2

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.061 MDCK Permeability:   -4.769
Pgp-inhibitor:   0.141 Pgp-substrate:   0.04
PAMPA:   0.871
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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):   0.182
20% Bioavailability (F20%):   0.983 30% Bioavailability (F30%):   0.998
50% Bioavailability (F50%):   0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.592
Plasma Protein Binding (PPB):   95.593% Volume Distribution (VD):   0.664
Fu: 4.521%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.863
OATP1B3 inhibitor:   0.891 BCRP inhibitor:   0.829
BSEP inhibitor:   0.978

ADMET: Metabolism

CYP1A2-inhibitor:   0.122 CYP1A2-substrate:   1.0
CYP2C19-inhibitor:   0.616 CYP2C19-substrate:   0.993
CYP2C9-inhibitor:   0.279 CYP2C9-substrate:   0.218
CYP2D6-inhibitor:   0.807 CYP2D6-substrate:   0.011
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   1.0
?
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):  11.925 Half-life (T1/2):  1.114

ADMET: Toxicity

hERG Blockers:  0.061 hERG Blockers (10um):  0.477
Human Hepatotoxicity (H-HT):  0.491 Drug-induced Liver Injury (DILI):  0.437
AMES Toxicity:  0.757 Rat Oral Acute Toxicity:  0.625
Maximum Recommended Daily Dose:  0.609 Skin Sensitization:  0.948
Carcinogencity:  0.453 Eye Corrosion:  0.01
Eye Irritation:  0.915 Respiratory Toxicity:  0.962
Drug-induced Neurotoxicity:  0.382 Ototoxicity:  0.369
Hematotoxicity:  0.191 Drug-induced Nephrotoxicity:  0.623
Genotoxicity:  0.787 RPMI-8226 Immunitoxicity:  0.126
A549 Cytotoxicity:  0.39 Hek293 Cytotoxicity:  0.512
BCF:   1.593
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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:   4.75
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.165
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.689
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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
NPO30824 Eurotium repens Species Aspergillaceae Eukaryota n.a. n.a. n.a. PMID[21667972]
NPO30824 Eurotium repens Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT271 Individual protein Delta opioid receptor Homo sapiens Activity < 40.0 % PMID[21667972]
NPT272 Individual protein Kappa opioid receptor Homo sapiens Activity < 40.0 % PMID[21667972]
NPT145 Individual protein Mu opioid receptor Homo sapiens Activity < 40.0 % PMID[21667972]
NPT232 Individual protein Cannabinoid CB1 receptor Homo sapiens Activity = 62.6 % PMID[21667972]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens Activity = 43.1 % PMID[21667972]
NPT232 Individual protein Cannabinoid CB1 receptor Homo sapiens IC50 = 15200.0 nM PMID[21667972]
NPT1287 Individual protein Cannabinoid CB2 receptor Homo sapiens IC50 = 19900.0 nM PMID[21667972]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT6 Organism Plasmodium falciparum Plasmodium falciparum IC50 = 1.1 ug.mL-1 PMID[23024574]
NPT554 Organism Candida glabrata Candida glabrata IC50 = 7.33 ug.mL-1 PMID[23024574]
NPT633 Organism Leishmania donovani Leishmania donovani IC50 = 7.5 ug.mL-1 PMID[23024574]
NPT187 Organism Issatchenkia orientalis Pichia kudriavzevii IC50 = 10.93 ug.mL-1 PMID[23024574]
NPT1666 Organism Plasmodium falciparum D6 Plasmodium falciparum D6 IC50 = 1.8 ug.mL-1 PMID[23024574]

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 NPC227741 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
0.7755 Intermediate Similarity NPC136342
0.6538 Remote Similarity NPC49647
0.5088 Remote Similarity NPC295202

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC227741 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