Natural Product: NPC119125

Natural Product IDNPC119125
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-3,5-Dimethoxygalloyl)-Beta-Dglucopyranoside
IUPAC Name [(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(3-hydroxy-4,5-dimethoxyphenoxy)oxan-2-yl]methyl 4-hydroxy-3,5-dimethoxybenzoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL1782850
PubChem CID 53356306
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 JWKGAUAMNHWOKC-PUIBNRJISA-N
Standard InCHI InChI=1S/C23H28O13/c1-30-13-5-10(6-14(31-2)17(13)25)22(29)34-9-16-18(26)19(27)20(28)23(36-16)35-11-7-12(24)21(33-4)15(8-11)32-3/h5-8,16,18-20,23-28H,9H2,1-4H3/t16-,18-,19+,20-,23-/m1/s1
SMILES COc1cc(cc(c1O)OC)C(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@H](Oc2cc(c(c(c2)OC)OC)O)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   512.15 Volume:   476.512
?
Van der Waals volume.
Dense:   1.075 LogP:   0.875
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.159
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.347
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   10.0 Rigid Bonds:   19.0
TPSA:   182.83
?
Topological Polar Surface Area.
 H-Bond Acceptor:   13.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   13.0

MedChem Properties

QED Drug-Likeness Score:   0.287 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.816 Fsp3:   0.435
MCE-18:   75.97
?
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:   Accepted BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.452 Fluc inhibitor:   0.039
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.174
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.622
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.137 Promiscuous compounds:   0.582

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.134 MDCK Permeability:   -5.306
Pgp-inhibitor:   0.094 Pgp-substrate:   0.263
PAMPA:   0.291
?
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):   0.155
20% Bioavailability (F20%):   0.293 30% Bioavailability (F30%):   0.386
50% Bioavailability (F50%):   0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.387 MRP1:   0.504
Plasma Protein Binding (PPB):   81.909% Volume Distribution (VD):   -0.361
Fu: 19.82%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.184
BSEP inhibitor:   0.251

ADMET: Metabolism

CYP1A2-inhibitor:   0.736 CYP1A2-substrate:   0.014
CYP2C19-inhibitor:   0.007 CYP2C19-substrate:   0.01
CYP2C9-inhibitor:   0.002 CYP2C9-substrate:   0.008
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.246
CYP3A4-inhibitor:   0.025 CYP3A4-substrate:   0.994
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.802
?
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):  2.521 Half-life (T1/2):  3.004

ADMET: Toxicity

hERG Blockers:  0.053 hERG Blockers (10um):  0.46
Human Hepatotoxicity (H-HT):  0.227 Drug-induced Liver Injury (DILI):  0.858
AMES Toxicity:  0.487 Rat Oral Acute Toxicity:  0.048
Maximum Recommended Daily Dose:  0.063 Skin Sensitization:  0.879
Carcinogencity:  0.258 Eye Corrosion:  0.0
Eye Irritation:  0.554 Respiratory Toxicity:  0.08
Drug-induced Neurotoxicity:  0.072 Ototoxicity:  0.661
Hematotoxicity:  0.089 Drug-induced Nephrotoxicity:  0.519
Genotoxicity:  0.022 RPMI-8226 Immunitoxicity:  0.281
A549 Cytotoxicity:  0.385 Hek293 Cytotoxicity:  0.268
BCF:   0.522
?
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:   3.279
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.551
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.846
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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 = 4.7 % 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 NPC119125 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 NPC311803
0.7183 Intermediate Similarity NPC5786
0.7042 Intermediate Similarity NPC102851
0.6761 Remote Similarity NPC197708
0.6618 Remote Similarity NPC166277
0.6522 Remote Similarity NPC472859
0.6429 Remote Similarity NPC25389
0.6324 Remote Similarity NPC469622
0.6316 Remote Similarity NPC602634
0.6301 Remote Similarity NPC327032
0.6197 Remote Similarity NPC1913
0.6154 Remote Similarity NPC485743
0.6076 Remote Similarity NPC658
0.5797 Remote Similarity NPC65833
0.5781 Remote Similarity NPC145900
0.5733 Remote Similarity NPC160780
0.5679 Remote Similarity NPC478797
0.5679 Remote Similarity NPC33298
0.5634 Remote Similarity NPC484156
0.5616 Remote Similarity NPC111785
0.5375 Remote Similarity NPC289346
0.5263 Remote Similarity NPC215811
0.5211 Remote Similarity NPC189589
0.5139 Remote Similarity NPC208769
0.5063 Remote Similarity NPC36130

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC119125 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