Natural Product: NPC53132

Natural Product IDNPC53132
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 CDEJOLJALIACLC-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 44259327
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones
          • [CHEMONTID:0001136] Flavonols

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 CDEJOLJALIACLC-UHFFFAOYSA-N
Standard InCHI InChI=1S/C19H16O8/c1-8(2)19(25)27-13-5-9(3-4-11(13)21)18-17(24)16(23)15-12(22)6-10(20)7-14(15)26-18/h3-8,20-22,24H,1-2H3
SMILES CC(C)C(=O)Oc1cc(ccc1O)c1c(c(=O)c2c(cc(cc2o1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   372.08 Volume:   358.104
?
Van der Waals volume.
Dense:   1.039 LogP:   2.646
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.386
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.275
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   4.0 Rigid Bonds:   19.0
TPSA:   137.43
?
Topological Polar Surface Area.
 H-Bond Acceptor:   8.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   8.0

MedChem Properties

QED Drug-Likeness Score:   0.407 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.692 Fsp3:   0.158
MCE-18:   21.0
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.728 Fluc inhibitor:   0.358
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.977
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.793
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.401 Promiscuous compounds:   0.51

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.59 MDCK Permeability:   -4.882
Pgp-inhibitor:   0.955 Pgp-substrate:   0.105
PAMPA:   0.559
?
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):   0.274
20% Bioavailability (F20%):   0.707 30% Bioavailability (F30%):   0.997
50% Bioavailability (F50%):   1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.769
Plasma Protein Binding (PPB):   98.214% Volume Distribution (VD):   -0.469
Fu: 1.427%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.87
OATP1B3 inhibitor:   0.998 BCRP inhibitor:   0.996
BSEP inhibitor:   0.979

ADMET: Metabolism

CYP1A2-inhibitor:   0.926 CYP1A2-substrate:   0.052
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.976
CYP2C9-inhibitor:   0.035 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.486 CYP2D6-substrate:   0.65
CYP3A4-inhibitor:   0.001 CYP3A4-substrate:   0.002
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.987
?
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):  4.988 Half-life (T1/2):  1.267

ADMET: Toxicity

hERG Blockers:  0.041 hERG Blockers (10um):  0.404
Human Hepatotoxicity (H-HT):  0.422 Drug-induced Liver Injury (DILI):  0.788
AMES Toxicity:  0.477 Rat Oral Acute Toxicity:  0.514
Maximum Recommended Daily Dose:  0.529 Skin Sensitization:  0.752
Carcinogencity:  0.403 Eye Corrosion:  0.506
Eye Irritation:  0.991 Respiratory Toxicity:  0.66
Drug-induced Neurotoxicity:  0.035 Ototoxicity:  0.126
Hematotoxicity:  0.097 Drug-induced Nephrotoxicity:  0.037
Genotoxicity:  0.916 RPMI-8226 Immunitoxicity:  0.061
A549 Cytotoxicity:  0.39 Hek293 Cytotoxicity:  0.598
BCF:   1.036
?
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:   3.752
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.699
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.25
?
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
NPO8355 Zaluzania triloba Species Asteraceae Eukaryota n.a. n.a. n.a. DOI[10.1016/S0040-4020(01)97900-1]
NPO9285 Eupatorium kiirunense Species Asteraceae Eukaryota n.a. Taiwan n.a. PMID[15921421]
NPO9285 Eupatorium kiirunense Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[15921421]
NPO10978 Annona senegalensis Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[7623038]
NPO10649 Guatteria ouregou Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[8676127]
NPO10978 Annona senegalensis Species Annonaceae Eukaryota n.a. n.a. n.a. PMID[8882434]
NPO8355 Zaluzania triloba Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO785 Nephroma parile Species Nephromataceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO285 Homeria glauca n.a. n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO10649 Guatteria ouregou Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9285 Eupatorium kiirunense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO11096 Earina autumnalis Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO10978 Annona senegalensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota Seed n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. Database[FooDB]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[Title]
NPO10649 Guatteria ouregou Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO2788 Virola surinamensis Species Myristicaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO11096 Earina autumnalis Species Orchidaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO785 Nephroma parile Species Nephromataceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO9285 Eupatorium kiirunense Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8355 Zaluzania triloba Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10978 Annona senegalensis Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO285 Homeria glauca 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

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference

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 NPC53132 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
0.7833 Intermediate Similarity NPC125062
0.6667 Remote Similarity NPC159103
0.6406 Remote Similarity NPC54394
0.6349 Remote Similarity NPC28274
0.623 Remote Similarity NPC179271
0.619 Remote Similarity NPC219330
0.6167 Remote Similarity NPC116775
0.6094 Remote Similarity NPC241838
0.6066 Remote Similarity NPC20791
0.6061 Remote Similarity NPC609179
0.597 Remote Similarity NPC252933
0.597 Remote Similarity NPC133953
0.5949 Remote Similarity NPC197285
0.5846 Remote Similarity NPC50403
0.5821 Remote Similarity NPC610401
0.5735 Remote Similarity NPC183950
0.5735 Remote Similarity NPC279989
0.5735 Remote Similarity NPC604021
0.5652 Remote Similarity NPC227192
0.5645 Remote Similarity NPC187432
0.5588 Remote Similarity NPC602125
0.5342 Remote Similarity NPC200694
0.5312 Remote Similarity NPC169749
0.5231 Remote Similarity NPC216361
0.5152 Remote Similarity NPC256042
0.5128 Remote Similarity NPC171821
0.5125 Remote Similarity NPC254306
0.5077 Remote Similarity NPC601197

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC53132 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
0.6066 Remote Similarity NPD1512 Phase 3

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