Natural Product: NPC218003

Natural Product IDNPC218003
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pinosilvin 3-O-Beta-D-Glucopyranoside
IUPAC Name (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[3-hydroxy-5-[(E)-2-phenylethenyl]phenoxy]oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL470251
PubChem CID 44559507
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 JTFNQPOMLDMAEW-GRHZDJGQSA-N
Standard InCHI InChI=1S/C20H22O7/c21-11-16-17(23)18(24)19(25)20(27-16)26-15-9-13(8-14(22)10-15)7-6-12-4-2-1-3-5-12/h1-10,16-25H,11H2/b7-6+/t16-,17-,18+,19-,20-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2cc(/C=C/c3ccccc3)cc(c2)O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   374.14 Volume:   371.883
?
Van der Waals volume.
Dense:   1.006 LogP:   2.423
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   2.525
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.749
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   5.0 Rigid Bonds:   19.0
TPSA:   119.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   3.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.49 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.579 Fsp3:   0.3
MCE-18:   60.923
?
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:   Rejected
Golden Triangle Rule:   Rejected BMS Rule:   0
Chelating Alert:   0 PAINS Alert:   0
Colloidal aggregators:   0.646 Fluc inhibitor:   0.981
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.142
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.393
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.445 Promiscuous compounds:   0.234

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.118 MDCK Permeability:   -5.141
Pgp-inhibitor:   0.0 Pgp-substrate:   0.019
PAMPA:   0.924
?
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):   0.078
20% Bioavailability (F20%):   0.561 30% Bioavailability (F30%):   0.981
50% Bioavailability (F50%):   0.961

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.2 MRP1:   0.037
Plasma Protein Binding (PPB):   86.719% Volume Distribution (VD):   -0.327
Fu: 15.378%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.998
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.07
BSEP inhibitor:   0.026

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.001
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.001
CYP2C9-inhibitor:   0.008 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.029 CYP2D6-substrate:   0.012
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.997
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   1.0
HLM stability:   0.046
?
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):  2.667 Half-life (T1/2):  2.804

ADMET: Toxicity

hERG Blockers:  0.091 hERG Blockers (10um):  0.318
Human Hepatotoxicity (H-HT):  0.791 Drug-induced Liver Injury (DILI):  0.528
AMES Toxicity:  0.829 Rat Oral Acute Toxicity:  0.037
Maximum Recommended Daily Dose:  0.105 Skin Sensitization:  0.988
Carcinogencity:  0.061 Eye Corrosion:  0.0
Eye Irritation:  0.783 Respiratory Toxicity:  0.02
Drug-induced Neurotoxicity:  0.057 Ototoxicity:  0.715
Hematotoxicity:  0.061 Drug-induced Nephrotoxicity:  0.721
Genotoxicity:  0.304 RPMI-8226 Immunitoxicity:  0.133
A549 Cytotoxicity:  0.591 Hek293 Cytotoxicity:  0.298
BCF:   0.866
?
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:   3.354
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.881
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   4.029
?
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
NPO32936 calligonum leucocladum Species Polygonaceae Eukaryota n.a. n.a. n.a. PMID[15217293]

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
NPT113 Cell line RAW264.7 Mus musculus IC50 = 12100.0 nM PMID[15387651]

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 NPC218003 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
0.8545 High Similarity NPC85799
0.8545 High Similarity NPC303422
0.8246 Intermediate Similarity NPC294166
0.8246 Intermediate Similarity NPC115022
0.7931 Intermediate Similarity NPC242028
0.7931 Intermediate Similarity NPC203230
0.7797 Intermediate Similarity NPC8497
0.7541 Intermediate Similarity NPC98777
0.7541 Intermediate Similarity NPC212770
0.6909 Remote Similarity NPC12308
0.678 Remote Similarity NPC214910
0.678 Remote Similarity NPC26080
0.678 Remote Similarity NPC165686
0.6667 Remote Similarity NPC185778
0.6066 Remote Similarity NPC479028
0.6066 Remote Similarity NPC479031
0.6061 Remote Similarity NPC260681
0.6056 Remote Similarity NPC188555
0.6 Remote Similarity NPC65530
0.5938 Remote Similarity NPC59324
0.5909 Remote Similarity NPC604095
0.5833 Remote Similarity NPC138350
0.5833 Remote Similarity NPC165482
0.5781 Remote Similarity NPC222455
0.5775 Remote Similarity NPC130496
0.5758 Remote Similarity NPC252169
0.5735 Remote Similarity NPC189115
0.5694 Remote Similarity NPC40664
0.5694 Remote Similarity NPC197723
0.5556 Remote Similarity NPC484946
0.5556 Remote Similarity NPC484951
0.5556 Remote Similarity NPC94045
0.5467 Remote Similarity NPC289346
0.5439 Remote Similarity NPC142319
0.5301 Remote Similarity NPC59692
0.5294 Remote Similarity NPC134260
0.5246 Remote Similarity NPC200092
0.5246 Remote Similarity NPC608788
0.5231 Remote Similarity NPC481303
0.5217 Remote Similarity NPC479374
0.5205 Remote Similarity NPC185103
0.5172 Remote Similarity NPC212729
0.5172 Remote Similarity NPC604498
0.5167 Remote Similarity NPC152722
0.5152 Remote Similarity NPC479029
0.5139 Remote Similarity NPC92054
0.5125 Remote Similarity NPC152346
0.5125 Remote Similarity NPC197703
0.5085 Remote Similarity NPC269242
0.5085 Remote Similarity NPC484157
0.5082 Remote Similarity NPC60589
0.5082 Remote Similarity NPC469708
0.5079 Remote Similarity NPC166168
0.5079 Remote Similarity NPC214454
0.507 Remote Similarity NPC475084

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC218003 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