Natural Product: NPC189115

Natural Product IDNPC189115
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 (2S,3R,4S,5S,6R)-2-[3-Hydroxy-5-[2-(3-Hydroxy-4-Methoxyphenyl)Ethyl]Phenoxy]-6-(Hydroxymethyl)Oxane-3,4,5-Triol
IUPAC Name (2S,3R,4S,5S,6R)-2-[3-hydroxy-5-[2-(3-hydroxy-4-methoxyphenyl)ethyl]phenoxy]-6-(hydroxymethyl)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL111185
PubChem CID 11430133
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000253] Stilbenes
        • [CHEMONTID:0000142] Stilbene 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 GDZSRLULWTWRJK-YMQHIKHWSA-N
Standard InCHI InChI=1S/C21H26O9/c1-28-16-5-4-11(8-15(16)24)2-3-12-6-13(23)9-14(7-12)29-21-20(27)19(26)18(25)17(10-22)30-21/h4-9,17-27H,2-3,10H2,1H3/t17-,18-,19+,20-,21-/m1/s1
SMILES COc1ccc(CCc2cc(cc(c2)O[C@H]2[C@@H]([C@H]([C@@H]([C@@H](CO)O2)O)O)O)O)cc1O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   422.16 Volume:   409.396
?
Van der Waals volume.
Dense:   1.031 LogP:   1.227
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   1.621
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The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -2.665
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The logarithm of aqueous solubility value.
Rotatable Bonds:   7.0 Rigid Bonds:   18.0
TPSA:   149.07
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Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   6.0 Rings:   3.0
Heavy Atoms:   9.0

MedChem Properties

QED Drug-Likeness Score:   0.364 GASA:   0.0
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GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.683 Fsp3:   0.429
MCE-18:   66.667
?
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:   0.505 Fluc inhibitor:   0.226
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The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.08
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.51
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.143 Promiscuous compounds:   0.197

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -5.834 MDCK Permeability:   -5.003
Pgp-inhibitor:   0.001 Pgp-substrate:   0.162
PAMPA:   0.927
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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):   0.521
20% Bioavailability (F20%):   0.647 30% Bioavailability (F30%):   0.983
50% Bioavailability (F50%):   0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.023 MRP1:   0.073
Plasma Protein Binding (PPB):   77.892% Volume Distribution (VD):   -0.297
Fu: 21.218%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   1.0
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.091
BSEP inhibitor:   0.017

ADMET: Metabolism

CYP1A2-inhibitor:   0.895 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.277 CYP2C19-substrate:   0.013
CYP2C9-inhibitor:   0.777 CYP2C9-substrate:   0.004
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.007
CYP3A4-inhibitor:   0.088 CYP3A4-substrate:   0.29
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.751
?
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):  3.824 Half-life (T1/2):  4.166

ADMET: Toxicity

hERG Blockers:  0.174 hERG Blockers (10um):  0.38
Human Hepatotoxicity (H-HT):  0.758 Drug-induced Liver Injury (DILI):  0.536
AMES Toxicity:  0.873 Rat Oral Acute Toxicity:  0.01
Maximum Recommended Daily Dose:  0.064 Skin Sensitization:  0.996
Carcinogencity:  0.101 Eye Corrosion:  0.0
Eye Irritation:  0.26 Respiratory Toxicity:  0.025
Drug-induced Neurotoxicity:  0.015 Ototoxicity:  0.958
Hematotoxicity:  0.245 Drug-induced Nephrotoxicity:  0.751
Genotoxicity:  0.251 RPMI-8226 Immunitoxicity:  0.128
A549 Cytotoxicity:  0.582 Hek293 Cytotoxicity:  0.588
BCF:   0.674
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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:   3.359
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.823
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.04
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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
NPO88 Rheum undulatum Species Polygonaceae Eukaryota rhizome n.a. n.a. PMID[10714491]
NPO88 Rheum undulatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO88 Rheum undulatum Species Polygonaceae Eukaryota n.a. n.a. n.a. Database[TM-MC]
NPO88 Rheum undulatum Species Polygonaceae 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
NPT32 Organism Mus musculus Mus musculus IC50 > 100000.0 nM PubChem BioAssay data set
NPT32 Organism Mus musculus Mus musculus Inhibition = 8.0 % PubChem BioAssay data set





 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 NPC189115 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
0.697 Remote Similarity NPC98777
0.6349 Remote Similarity NPC19470
0.6333 Remote Similarity NPC12308
0.6269 Remote Similarity NPC294166
0.6269 Remote Similarity NPC115022
0.6232 Remote Similarity NPC210192
0.6232 Remote Similarity NPC212770
0.614 Remote Similarity NPC116907
0.6029 Remote Similarity NPC469661
0.5942 Remote Similarity NPC185778
0.5735 Remote Similarity NPC85799
0.5735 Remote Similarity NPC303422
0.5735 Remote Similarity NPC218003
0.5714 Remote Similarity NPC8497
0.5645 Remote Similarity NPC60589
0.5645 Remote Similarity NPC469708
0.5606 Remote Similarity NPC472024
0.5606 Remote Similarity NPC270849
0.5571 Remote Similarity NPC242028
0.5571 Remote Similarity NPC203230
0.5556 Remote Similarity NPC475096
0.5556 Remote Similarity NPC106944
0.5522 Remote Similarity NPC26653
0.5522 Remote Similarity NPC210015
0.5522 Remote Similarity NPC80600
0.55 Remote Similarity NPC245615
0.5469 Remote Similarity NPC221090
0.5469 Remote Similarity NPC145900
0.5405 Remote Similarity NPC116229
0.5395 Remote Similarity NPC488085
0.5385 Remote Similarity NPC5778
0.5362 Remote Similarity NPC222455
0.5352 Remote Similarity NPC134260
0.5325 Remote Similarity NPC279298
0.5325 Remote Similarity NPC147596
0.5323 Remote Similarity NPC192810
0.5303 Remote Similarity NPC310661
0.5303 Remote Similarity NPC9912
0.5294 Remote Similarity NPC481303
0.5286 Remote Similarity NPC59324
0.5246 Remote Similarity NPC142319
0.5238 Remote Similarity NPC152722
0.5217 Remote Similarity NPC105827
0.5211 Remote Similarity NPC100389
0.5195 Remote Similarity NPC61594
0.5156 Remote Similarity NPC609376
0.5147 Remote Similarity NPC205054
0.5147 Remote Similarity NPC23084
0.5128 Remote Similarity NPC227902
0.5128 Remote Similarity NPC56735
0.5125 Remote Similarity NPC298847
0.5072 Remote Similarity NPC26080
0.5072 Remote Similarity NPC165686
0.5068 Remote Similarity NPC111536
0.5068 Remote Similarity NPC186418
0.5068 Remote Similarity NPC604095
0.5065 Remote Similarity NPC191046

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC189115 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