Natural Product: NPC295406

Natural Product IDNPC295406
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Gentiside J
IUPAC Name docosyl 2,3-dihydroxybenzoate
Synonyms Gentiside J
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1254431
PubChem CID 14177660
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0002448] Benzenoids
      • [CHEMONTID:0002279] Benzene and substituted derivatives
        • [CHEMONTID:0000176] Benzoic acids and derivatives
          • [CHEMONTID:0001350] Benzoic acid esters
            • [CHEMONTID:0004699] m-Hydroxybenzoic acid esters

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 ZYHQORYZNVHDNT-UHFFFAOYSA-N
Standard InCHI InChI=1S/C29H50O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-25-33-29(32)26-23-22-24-27(30)28(26)31/h22-24,30-31H,2-21,25H2,1H3
SMILES CCCCCCCCCCCCCCCCCCCCCCOC(=O)c1cccc(c1O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   462.37 Volume:   526.199
?
Van der Waals volume.
Dense:   0.879 LogP:   9.144
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   4.666
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -6.461
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   23.0 Rigid Bonds:   7.0
TPSA:   66.76
?
Topological Polar Surface Area.
 H-Bond Acceptor:   4.0
H-Bond Donor:   2.0 Rings:   1.0
Heavy Atoms:   4.0

MedChem Properties

QED Drug-Likeness Score:   0.102 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   2.242 Fsp3:   0.759
MCE-18:   7.0
?
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:   1 PAINS Alert:   1
Colloidal aggregators:   0.713 Fluc inhibitor:   0.377
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.049
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.136
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.792 Promiscuous compounds:   0.359

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.079 MDCK Permeability:   -4.879
Pgp-inhibitor:   0.0 Pgp-substrate:   0.002
PAMPA:   0.0
?
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):   0.892
20% Bioavailability (F20%):   0.997 30% Bioavailability (F30%):   1.0
50% Bioavailability (F50%):   0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.002 MRP1:   0.998
Plasma Protein Binding (PPB):   99.848% Volume Distribution (VD):   1.416
Fu: 0.686%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.635
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.788
BSEP inhibitor:   0.319

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.992
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.371
CYP2C9-inhibitor:   0.646 CYP2C9-substrate:   0.525
CYP2D6-inhibitor:   0.229 CYP2D6-substrate:   0.731
CYP3A4-inhibitor:   0.02 CYP3A4-substrate:   1.0
CYP2B6-substrate:   0.001 CYP2C8-inhibitor:   1.0
HLM stability:   0.593
?
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):  4.701 Half-life (T1/2):  2.471

ADMET: Toxicity

hERG Blockers:  0.671 hERG Blockers (10um):  0.968
Human Hepatotoxicity (H-HT):  0.085 Drug-induced Liver Injury (DILI):  0.116
AMES Toxicity:  0.011 Rat Oral Acute Toxicity:  0.072
Maximum Recommended Daily Dose:  0.222 Skin Sensitization:  0.996
Carcinogencity:  0.486 Eye Corrosion:  0.731
Eye Irritation:  0.998 Respiratory Toxicity:  0.924
Drug-induced Neurotoxicity:  0.002 Ototoxicity:  0.096
Hematotoxicity:  0.004 Drug-induced Nephrotoxicity:  0.012
Genotoxicity:  0.0 RPMI-8226 Immunitoxicity:  0.051
A549 Cytotoxicity:  0.964 Hek293 Cytotoxicity:  0.541
BCF:   0.125
?
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:   4.784
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   6.572
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.895
?
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
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota roots n.a. n.a. PMID[17375953]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. PMID[20813533]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. stem n.a. PMID[21043460]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. PMID[21043460]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. leaf n.a. PMID[21043460]
NPO27624 Swartzia simplex Species Fabaceae Eukaryota n.a. n.a. n.a. PMID[26654828]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[32372353]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[33588649]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. PMID[37849964]
NPO12009 Abies pinsapo Species Pinaceae Eukaryota Wood n.a. n.a. PMID[7931362]
NPO17054 Streptomyces gardneri Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17368 Erythrina senegalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15518 Streptomyces netropsis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[COCONUT]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO17699 Solanum glaucophyllum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16817 Aglaia argentea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15856 Podocarpus hallii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16958 Jurinea albicaulis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO19120 Strychnos aculeata Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO17368 Erythrina senegalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO15856 Podocarpus hallii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO15856 Podocarpus hallii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO17368 Erythrina senegalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO16817 Aglaia argentea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO19120 Strychnos aculeata Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO15856 Podocarpus hallii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO16958 Jurinea albicaulis Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO13251 Iris nertchinskia Species Tarachodidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16817 Aglaia argentea Species Meliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18843 Antirrhinum majus Species Plantaginaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18372 Lobophytum crassospiculatum Species Alcyoniidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18511 Latimeria chalumnae Species Coelacanthidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17699 Solanum glaucophyllum Species Solanaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17493 Alstonia spatulata Species Apocynaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16073 Sarcomelicope megistophylla Species Rutaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO27624 Swartzia simplex Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17368 Erythrina senegalensis Species Fabaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO12009 Abies pinsapo Species Pinaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO19120 Strychnos aculeata Species Loganiaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15856 Podocarpus hallii Species Podocarpaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15518 Streptomyces netropsis Species Streptomycetaceae Bacteria n.a. n.a. n.a. Database[UNPD]
NPO17711 Sphenoclea zeylanica Species Sphenocleaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO16646 Artemisia campestris Species Asteraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO14721 Dentitheca habereri Species Plumulariidae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO18234 Gentiana rigescens Species Gentianaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO3046 Schisandra bicolor Species Schisandraceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO17054 Streptomyces gardneri Species Streptomycetaceae Bacteria 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
NPT681 Cell line PC-12 Rattus norvegicus Activity = 67.0 % PMID[20813533]

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 NPC295406 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
1.0 High Similarity NPC200422
1.0 High Similarity NPC289572
1.0 High Similarity NPC157478
0.8409 Intermediate Similarity NPC254832
0.8409 Intermediate Similarity NPC29317
0.8043 Intermediate Similarity NPC71108
0.8043 Intermediate Similarity NPC204257
0.8043 Intermediate Similarity NPC267539
0.8043 Intermediate Similarity NPC229638
0.8043 Intermediate Similarity NPC176102
0.6667 Remote Similarity NPC90522
0.6222 Remote Similarity NPC607895
0.587 Remote Similarity NPC156892
0.5682 Remote Similarity NPC93084
0.5682 Remote Similarity NPC251854
0.5682 Remote Similarity NPC78701
0.5682 Remote Similarity NPC601045
0.5319 Remote Similarity NPC604243

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC295406 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