Natural Product: NPC289771

Natural Product IDNPC289771
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Quercetin-6-C-Beta-D-Glucopyranoside
IUPAC Name 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-6-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL561741
PubChem CID 21676320
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001737] Flavonoid C-glycosides

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 IDPMRJRWHIXCDU-DSTJRUDUSA-N
Standard InCHI InChI=1S/C21H20O12/c22-5-11-14(26)17(29)19(31)21(33-11)12-9(25)4-10-13(15(12)27)16(28)18(30)20(32-10)6-1-2-7(23)8(24)3-6/h1-4,11,14,17,19,21-27,29-31H,5H2/t11-,14-,17+,19-,21+/m1/s1
SMILES OC[C@H]1O[C@H]([C@@H]([C@H]([C@@H]1O)O)O)c1c(O)cc2c(c1O)c(=O)c(c(o2)c1ccc(c(c1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   464.1 Volume:   421.937
?
Van der Waals volume.
Dense:   1.1 LogP:   0.0
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.646
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.94
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   221.51
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   9.0 Rings:   4.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.224 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.159 Fsp3:   0.286
MCE-18:   94.37
?
MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.
 Lipinski Rule-of-5:   Accepted
Pfizer Rule:   Rejected GSK Rule:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   1
Chelating Alert:   1 PAINS Alert:   1
Colloidal aggregators:   0.705 Fluc inhibitor:   0.211
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.877
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.57
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.313 Promiscuous compounds:   0.64

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.325 MDCK Permeability:   -4.851
Pgp-inhibitor:   0.0 Pgp-substrate:   0.074
PAMPA:   0.999
?
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):   0.95
20% Bioavailability (F20%):   0.561 30% Bioavailability (F30%):   0.999
50% Bioavailability (F50%):   0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.744
Plasma Protein Binding (PPB):   85.931% Volume Distribution (VD):   -0.236
Fu: 10.403%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.26
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.255
BSEP inhibitor:   0.016

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.001 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.014
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.968
HLM stability:   0.357
?
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):  4.128 Half-life (T1/2):  4.863

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.168
Human Hepatotoxicity (H-HT):  0.449 Drug-induced Liver Injury (DILI):  0.905
AMES Toxicity:  0.753 Rat Oral Acute Toxicity:  0.092
Maximum Recommended Daily Dose:  0.164 Skin Sensitization:  0.995
Carcinogencity:  0.169 Eye Corrosion:  0.0
Eye Irritation:  0.874 Respiratory Toxicity:  0.044
Drug-induced Neurotoxicity:  0.001 Ototoxicity:  0.827
Hematotoxicity:  0.049 Drug-induced Nephrotoxicity:  0.056
Genotoxicity:  0.898 RPMI-8226 Immunitoxicity:  0.044
A549 Cytotoxicity:  0.725 Hek293 Cytotoxicity:  0.283
BCF:   0.498
?
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:   3.05
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.506
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.836
?
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
NPO7764 Ulmus wallichiana Species Ulmaceae Eukaryota n.a. n.a. n.a. PMID[19596573]
NPO24507 Kalmia angustifolia Species Ericaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO15288 Zelkova serrata Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23797 Skimmia reevesiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO23797 Skimmia reevesiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[HerDing]
NPO23797 Skimmia reevesiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCMID]
NPO23797 Skimmia reevesiana Species Rutaceae Eukaryota n.a. n.a. n.a. Database[TCM_Taiwan]
NPO7764 Ulmus wallichiana Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10904 Panax arboreus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO24507 Kalmia angustifolia Species Ericaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15288 Zelkova serrata Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO23797 Skimmia reevesiana Species Rutaceae 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
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 15.6 % PMID[21129962]
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 8.56 % PMID[21129962]





 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 NPC289771 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
0.8769 High Similarity NPC268193
0.7971 Intermediate Similarity NPC53545
0.7083 Intermediate Similarity NPC328740
0.7083 Intermediate Similarity NPC289774
0.6506 Remote Similarity NPC218488
0.6377 Remote Similarity NPC10097
0.6375 Remote Similarity NPC111249
0.6282 Remote Similarity NPC304745
0.589 Remote Similarity NPC139966
0.5867 Remote Similarity NPC228383
0.5867 Remote Similarity NPC239644
0.5814 Remote Similarity NPC47923
0.5769 Remote Similarity NPC117418
0.5698 Remote Similarity NPC603300
0.55 Remote Similarity NPC112701
0.5342 Remote Similarity NPC157784
0.5281 Remote Similarity NPC78734
0.519 Remote Similarity NPC471789
0.5181 Remote Similarity NPC277205
0.5181 Remote Similarity NPC37919
0.5119 Remote Similarity NPC245014
0.5062 Remote Similarity NPC209846
0.5059 Remote Similarity NPC117260
0.5057 Remote Similarity NPC326592
0.5055 Remote Similarity NPC607513

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC289771 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