Natural Product: NPC304342

Natural Product IDNPC304342
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 VSHICDFQSGJNPK-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier n.a.
PubChem CID 15293760
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001615] Flavones

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 VSHICDFQSGJNPK-UHFFFAOYSA-N
Standard InCHI InChI=1S/C16H12O6/c1-7-10(18)5-14-15(16(7)21)12(20)6-13(22-14)8-2-3-9(17)11(19)4-8/h2-6,17-19,21H,1H3
SMILES Cc1c(cc2c(c(=O)cc(c3ccc(c(c3)O)O)o2)c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   300.06 Volume:   291.273
?
Van der Waals volume.
Dense:   1.03 LogP:   2.515
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.115
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.057
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   1.0 Rigid Bonds:   18.0
TPSA:   111.13
?
Topological Polar Surface Area.
 H-Bond Acceptor:   6.0
H-Bond Donor:   4.0 Rings:   3.0
Heavy Atoms:   6.0

MedChem Properties

QED Drug-Likeness Score:   0.514 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.536 Fsp3:   0.062
MCE-18:   19.0
?
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:   1
Colloidal aggregators:   0.885 Fluc inhibitor:   0.8
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.984
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.628
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.567 Promiscuous compounds:   0.715

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.023 MDCK Permeability:   -4.74
Pgp-inhibitor:   0.009 Pgp-substrate:   0.05
PAMPA:   0.551
?
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):   0.014
20% Bioavailability (F20%):   0.91 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.008 MRP1:   0.888
Plasma Protein Binding (PPB):   97.091% Volume Distribution (VD):   -0.497
Fu: 2.711%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.984
OATP1B3 inhibitor:   0.99 BCRP inhibitor:   0.752
BSEP inhibitor:   0.307

ADMET: Metabolism

CYP1A2-inhibitor:   0.392 CYP1A2-substrate:   0.021
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.322 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.997 CYP2D6-substrate:   0.999
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.258
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.586
?
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):  11.037 Half-life (T1/2):  1.407

ADMET: Toxicity

hERG Blockers:  0.042 hERG Blockers (10um):  0.546
Human Hepatotoxicity (H-HT):  0.393 Drug-induced Liver Injury (DILI):  0.664
AMES Toxicity:  0.639 Rat Oral Acute Toxicity:  0.545
Maximum Recommended Daily Dose:  0.812 Skin Sensitization:  0.962
Carcinogencity:  0.566 Eye Corrosion:  0.396
Eye Irritation:  0.998 Respiratory Toxicity:  0.911
Drug-induced Neurotoxicity:  0.013 Ototoxicity:  0.225
Hematotoxicity:  0.057 Drug-induced Nephrotoxicity:  0.017
Genotoxicity:  0.984 RPMI-8226 Immunitoxicity:  0.039
A549 Cytotoxicity:  0.712 Hek293 Cytotoxicity:  0.643
BCF:   1.134
?
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:   3.999
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.774
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.394
?
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
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. tenerife n.a. PMID[10924166]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[16309323]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[22220686]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. PMID[24279991]
NPO13803 Neopetrosia exigua Species Petrosiidae Eukaryota n.a. n.a. n.a. PMID[24784222]
NPO16201 Pteris altissima Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18716 Parmelia caraccensis Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO13803 Neopetrosia exigua Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17606 Millettia ichthyochtona Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17281 Echinaster echinophorus Species Echinasteridae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18250 Conus tessulatus Species Conidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO19061 Ceratozamia kuesteriana Species Zamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17281 Echinaster echinophorus Species Echinasteridae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13803 Neopetrosia exigua Species Petrosiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19061 Ceratozamia kuesteriana Species Zamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18716 Parmelia caraccensis Species Parmeliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18850 Aplysia dactylomela Species Aplysiidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18250 Conus tessulatus Species Conidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16201 Pteris altissima Species Pteridaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17606 Millettia ichthyochtona Species Fabaceae 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

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 NPC304342 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
0.76 Intermediate Similarity NPC201395
0.7018 Intermediate Similarity NPC3825
0.6538 Remote Similarity NPC275772
0.6415 Remote Similarity NPC279121
0.625 Remote Similarity NPC100887
0.6119 Remote Similarity NPC476280
0.5893 Remote Similarity NPC473042
0.5882 Remote Similarity NPC53545
0.5882 Remote Similarity NPC66809
0.5882 Remote Similarity NPC46736
0.5882 Remote Similarity NPC197856
0.5789 Remote Similarity NPC482122
0.5741 Remote Similarity NPC118726
0.5738 Remote Similarity NPC284220
0.5636 Remote Similarity NPC70136
0.5625 Remote Similarity NPC476283
0.5593 Remote Similarity NPC108406
0.5593 Remote Similarity NPC25270
0.5593 Remote Similarity NPC162313
0.5556 Remote Similarity NPC476295
0.5556 Remote Similarity NPC486096
0.5469 Remote Similarity NPC603717
0.5455 Remote Similarity NPC17286
0.5385 Remote Similarity NPC59210
0.5385 Remote Similarity NPC108113
0.5385 Remote Similarity NPC189706
0.5357 Remote Similarity NPC130230
0.5333 Remote Similarity NPC78913
0.5333 Remote Similarity NPC605047
0.5238 Remote Similarity NPC88804
0.5195 Remote Similarity NPC294629
0.5195 Remote Similarity NPC131407
0.5179 Remote Similarity NPC50898
0.5167 Remote Similarity NPC188203
0.5088 Remote Similarity NPC175013
0.5082 Remote Similarity NPC201136
0.5082 Remote Similarity NPC604569
0.5072 Remote Similarity NPC602497

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC304342 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
0.6415 Remote Similarity NPD1511 Phase 2

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