Natural Product: NPC47152

Natural Product IDNPC47152
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 LVOXAJYEGVDSQA-UHFFFAOYSA-N
IUPAC Name n.a.
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL88230
PubChem CID 196959
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0000023] Naphthalenes

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 LVOXAJYEGVDSQA-UHFFFAOYSA-N
Standard InCHI InChI=1S/C20H12O4/c21-14-7-3-6-13-19(14)15(22)10-11-20(13)23-16-8-1-4-12-5-2-9-17(24-20)18(12)16/h1-11,21H
SMILES c1cc2cccc3c2c(c1)OC1(C=CC(=O)c2c1cccc2O)O3

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   316.07 Volume:   320.49
?
Van der Waals volume.
Dense:   0.986 LogP:   3.503
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   3.401
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -4.63
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   0.0 Rigid Bonds:   27.0
TPSA:   55.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   1.0 Rings:   5.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.683 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.331 Fsp3:   0.05
MCE-18:   80.476
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.957 Fluc inhibitor:   0.783
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.985
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.86
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.942 Promiscuous compounds:   0.182

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -4.829 MDCK Permeability:   -4.734
Pgp-inhibitor:   0.023 Pgp-substrate:   0.027
PAMPA:   0.335
?
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%):   0.068 30% Bioavailability (F30%):   0.346
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.96 MRP1:   0.607
Plasma Protein Binding (PPB):   98.356% Volume Distribution (VD):   -0.287
Fu: 0.892%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.663
OATP1B3 inhibitor:   0.977 BCRP inhibitor:   0.004
BSEP inhibitor:   0.994

ADMET: Metabolism

CYP1A2-inhibitor:   0.963 CYP1A2-substrate:   0.999
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.104
CYP2C9-inhibitor:   0.996 CYP2C9-substrate:   0.471
CYP2D6-inhibitor:   0.636 CYP2D6-substrate:   0.939
CYP3A4-inhibitor:   0.058 CYP3A4-substrate:   0.995
CYP2B6-substrate:   0.002 CYP2C8-inhibitor:   0.994
HLM stability:   0.992
?
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):  1.798 Half-life (T1/2):  1.027

ADMET: Toxicity

hERG Blockers:  0.113 hERG Blockers (10um):  0.546
Human Hepatotoxicity (H-HT):  0.61 Drug-induced Liver Injury (DILI):  0.796
AMES Toxicity:  0.837 Rat Oral Acute Toxicity:  0.719
Maximum Recommended Daily Dose:  0.302 Skin Sensitization:  0.712
Carcinogencity:  0.643 Eye Corrosion:  0.008
Eye Irritation:  0.912 Respiratory Toxicity:  0.98
Drug-induced Neurotoxicity:  0.282 Ototoxicity:  0.331
Hematotoxicity:  0.372 Drug-induced Nephrotoxicity:  0.582
Genotoxicity:  0.43 RPMI-8226 Immunitoxicity:  0.186
A549 Cytotoxicity:  0.287 Hek293 Cytotoxicity:  0.57
BCF:   1.787
?
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:   4.644
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.034
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   5.388
?
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
NPO20809 Sarcophyton trocheliophorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[10923847]
NPO22513 Decaisnella thyridioides Species n.a. n.a. n.a. n.a. n.a. PMID[17190439]
NPO27979 Guatteria friesiana Species Annonaceae Eukaryota Stems n.a. n.a. PMID[19639965]
NPO20809 Sarcophyton trocheliophorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. PMID[23859780]
NPO40437 Anteaglonium sp. FL0768 Strain Anteagloniaceae Eukaryota n.a. n.a. n.a. PMID[26539727]
NPO27979 Guatteria friesiana Species Annonaceae Eukaryota Barks n.a. n.a. PMID[27300257]
NPO22585 Thymus striatus Species Lamiaceae Eukaryota n.a. n.a. n.a. PMID[34405529]
NPO18233 Capparis sepiaria Species Capparaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23674 Jatropha curcas Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20809 Sarcophyton trocheliophorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23179 Penicillium paraherquei Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21115 Crepidiastrum keiskeanum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO20542 Vellozia phalocarpa Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO22513 Decaisnella thyridioides Species n.a. n.a. n.a. n.a. n.a. Database[COCONUT]
NPO28371 Echinodontium japonicum Species Echinodontiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO21512 Salvia cardiophylla Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO40437 Anteaglonium sp. FL0768 Strain Anteagloniaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23674 Jatropha curcas Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23674 Jatropha curcas Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23674 Jatropha curcas Species Euphorbiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20220 Coccus citri Species Coccidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23179 Penicillium paraherquei Species Aspergillaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10812 Beaucarnea hookeri Species Asparagaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO8904 Oreocnide frutescens Species Urticaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO26602 Ranunculus cantoniensis Species Ranunculaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22387 Guettarda speciosa Species Rubiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22585 Thymus striatus Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21512 Salvia cardiophylla Species Lamiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27979 Guatteria friesiana Species Annonaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22513 Decaisnella thyridioides Species n.a. n.a. n.a. n.a. n.a. Database[UNPD]
NPO2283 Epichloe uncinata Species Clavicipitaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20542 Vellozia phalocarpa Species Velloziaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19400 Cussonia natalensis Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22325 Caesalpinia sepiaria Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18233 Capparis sepiaria Species Capparaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21115 Crepidiastrum keiskeanum Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17178 Labisia pumila Species Primulaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO28371 Echinodontium japonicum Species Echinodontiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO20809 Sarcophyton trocheliophorum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO21877 Aplysilla violacea Species Darwinellidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO22001 Delphinus longirostris Species Delphinidae 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
NPT3005 Protein family Thioredoxin reductase Homo sapiens IC50 = 12000.0 nM PMID[11551767]
NPT3005 Protein family Thioredoxin reductase Homo sapiens IC50 = 350.0 nM PMID[11551767]

In vitro activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT82 Cell line MDA-MB-231 Homo sapiens IC50 = 2400.0 nM PMID[11551767]
NPT83 Cell line MCF7 Homo sapiens IC50 = 1000.0 nM PMID[11551767]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 1600.0 nM PMID[26539727]

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 NPC47152 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
0.5932 Remote Similarity NPC306816
0.5645 Remote Similarity NPC472159
0.5161 Remote Similarity NPC138940
0.5079 Remote Similarity NPC485851

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC47152 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