Natural Product: NPC311803

Natural Product IDNPC311803
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 1-O-3,4-Dimethoxy-5-Hydroxyphenyl-(6-O-Vanilloyl)-Beta-D-Glucopyranoside
IUPAC Name [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(3-hydroxy-4,5-dimethoxyphenoxy)oxan-2-yl]methyl 4-hydroxy-3-methoxybenzoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1782851
PubChem CID 53356307
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000238] Tannins
        • [CHEMONTID:0001710] Hydrolyzable tannins

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 WCXHEUMNHRAWIJ-NFSXTHTRSA-N
Standard InCHI InChI=1S/C22H26O12/c1-29-14-6-10(4-5-12(14)23)21(28)32-9-16-17(25)18(26)19(27)22(34-16)33-11-7-13(24)20(31-3)15(8-11)30-2/h4-8,16-19,22-27H,9H2,1-3H3/t16-,17-,18+,19-,22-/m1/s1
SMILES COc1cc(O[C@@H]2O[C@H](COC(=O)c3ccc(c(c3)OC)O)[C@H]([C@@H]([C@H]2O)O)O)cc(c1OC)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   482.14 Volume:   450.426
?
Van der Waals volume.
Dense:   1.07 LogP:   0.934
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.253
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.434
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   9.0 Rigid Bonds:   19.0
TPSA:   173.6
?
Topological Polar Surface Area.
 H-Bond Acceptor:   12.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   12.0

MedChem Properties

QED Drug-Likeness Score:   0.323 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.727 Fsp3:   0.409
MCE-18:   73.097
?
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:   Accepted
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.476 Fluc inhibitor:   0.148
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.138
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.613
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.125 Promiscuous compounds:   0.551

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.132 MDCK Permeability:   -5.209
Pgp-inhibitor:   0.004 Pgp-substrate:   0.166
PAMPA:   0.599
?
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):   0.087
20% Bioavailability (F20%):   0.654 30% Bioavailability (F30%):   0.762
50% Bioavailability (F50%):   0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.057 MRP1:   0.868
Plasma Protein Binding (PPB):   78.023% Volume Distribution (VD):   -0.27
Fu: 23.111%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.277
BSEP inhibitor:   0.142

ADMET: Metabolism

CYP1A2-inhibitor:   0.534 CYP1A2-substrate:   0.009
CYP2C19-inhibitor:   0.004 CYP2C19-substrate:   0.016
CYP2C9-inhibitor:   0.015 CYP2C9-substrate:   0.002
CYP2D6-inhibitor:   0.01 CYP2D6-substrate:   0.22
CYP3A4-inhibitor:   0.014 CYP3A4-substrate:   0.996
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.987
HLM stability:   0.718
?
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):  2.731 Half-life (T1/2):  2.675

ADMET: Toxicity

hERG Blockers:  0.06 hERG Blockers (10um):  0.512
Human Hepatotoxicity (H-HT):  0.205 Drug-induced Liver Injury (DILI):  0.787
AMES Toxicity:  0.533 Rat Oral Acute Toxicity:  0.039
Maximum Recommended Daily Dose:  0.064 Skin Sensitization:  0.923
Carcinogencity:  0.242 Eye Corrosion:  0.001
Eye Irritation:  0.693 Respiratory Toxicity:  0.07
Drug-induced Neurotoxicity:  0.056 Ototoxicity:  0.6
Hematotoxicity:  0.051 Drug-induced Nephrotoxicity:  0.503
Genotoxicity:  0.032 RPMI-8226 Immunitoxicity:  0.229
A549 Cytotoxicity:  0.397 Hek293 Cytotoxicity:  0.315
BCF:   0.535
?
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:   3.186
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.483
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.823
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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
NPO31118 Gordonia chrysandra Species Theaceae Eukaryota Roots Yunnan Province, China 2005-MAY PMID[20560647]
NPO31118 Gordonia chrysandra Species Theaceae Eukaryota n.a. stem n.a. PMID[21473609]
NPO31118 Gordonia chrysandra Species Theaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]

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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Inhibition = 6.5 % PMID[21473609]

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 NPC311803 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
0.8594 High Similarity NPC119125
0.7429 Intermediate Similarity NPC327032
0.7123 Intermediate Similarity NPC5786
0.6757 Remote Similarity NPC102851
0.662 Remote Similarity NPC25389
0.6338 Remote Similarity NPC166277
0.6267 Remote Similarity NPC197708
0.625 Remote Similarity NPC472859
0.6056 Remote Similarity NPC469622
0.6 Remote Similarity NPC65833
0.5946 Remote Similarity NPC1913
0.5875 Remote Similarity NPC194095
0.575 Remote Similarity NPC485234
0.5714 Remote Similarity NPC160780
0.5663 Remote Similarity NPC658
0.5663 Remote Similarity NPC33298
0.5647 Remote Similarity NPC476011
0.56 Remote Similarity NPC111785
0.5591 Remote Similarity NPC316539
0.5556 Remote Similarity NPC289346
0.5522 Remote Similarity NPC145900
0.5488 Remote Similarity NPC602634
0.5455 Remote Similarity NPC215811
0.5405 Remote Similarity NPC484156
0.5366 Remote Similarity NPC472860
0.5366 Remote Similarity NPC484816
0.5357 Remote Similarity NPC485743
0.5222 Remote Similarity NPC133984
0.5132 Remote Similarity NPC37074
0.5125 Remote Similarity NPC191046
0.5116 Remote Similarity NPC478797
0.5106 Remote Similarity NPC163165
0.5065 Remote Similarity NPC287780
0.5065 Remote Similarity NPC60982
0.5063 Remote Similarity NPC4958
0.5062 Remote Similarity NPC36130
0.5059 Remote Similarity NPC471405

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC311803 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