Natural Product: NPC9248

Natural Product IDNPC9248
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Pyrocatechol-O-Beta-D-Glucopyranoside
IUPAC Name (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-(2-hydroxyphenoxy)oxane-3,4,5-triol
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL443206
PubChem CID 9900144
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0004603] Organic oxygen compounds
      • [CHEMONTID:0000323] Organooxygen compounds
        • [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates
          • [CHEMONTID:0002105] Glycosyl compounds
            • [CHEMONTID:0004165] Phenolic 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 NMZWIAATAZXMRV-RMPHRYRLSA-N
Standard InCHI InChI=1S/C12H16O7/c13-5-8-9(15)10(16)11(17)12(19-8)18-7-4-2-1-3-6(7)14/h1-4,8-17H,5H2/t8-,9-,10+,11-,12-/m1/s1
SMILES OC[C@H]1O[C@@H](Oc2ccccc2O)[C@@H]([C@H]([C@@H]1O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   272.09 Volume:   252.618
?
Van der Waals volume.
Dense:   1.077 LogP:   -0.527
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   -0.134
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.109
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   12.0
TPSA:   119.61
?
Topological Polar Surface Area.
 H-Bond Acceptor:   7.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   7.0

MedChem Properties

QED Drug-Likeness Score:   0.457 GASA:   0.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   3.371 Fsp3:   0.5
MCE-18:   46.222
?
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:   1 PAINS Alert:   0
Colloidal aggregators:   0.435 Fluc inhibitor:   0.003
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.128
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.018
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.41 Promiscuous compounds:   0.295

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.439 MDCK Permeability:   -5.024
Pgp-inhibitor:   0.0 Pgp-substrate:   0.238
PAMPA:   0.964
?
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):   0.888
20% Bioavailability (F20%):   0.625 30% Bioavailability (F30%):   0.979
50% Bioavailability (F50%):   0.954

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.679 MRP1:   0.087
Plasma Protein Binding (PPB):   53.816% Volume Distribution (VD):   -0.399
Fu: 48.013%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.982
OATP1B3 inhibitor:   0.991 BCRP inhibitor:   0.096
BSEP inhibitor:   0.003

ADMET: Metabolism

CYP1A2-inhibitor:   0.001 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.003
CYP2C9-inhibitor:   0.284 CYP2C9-substrate:   0.003
CYP2D6-inhibitor:   0.001 CYP2D6-substrate:   0.0
CYP3A4-inhibitor:   0.094 CYP3A4-substrate:   0.655
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.58
HLM stability:   0.106
?
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):  2.34 Half-life (T1/2):  2.373

ADMET: Toxicity

hERG Blockers:  0.013 hERG Blockers (10um):  0.238
Human Hepatotoxicity (H-HT):  0.441 Drug-induced Liver Injury (DILI):  0.369
AMES Toxicity:  0.745 Rat Oral Acute Toxicity:  0.057
Maximum Recommended Daily Dose:  0.017 Skin Sensitization:  0.967
Carcinogencity:  0.12 Eye Corrosion:  0.005
Eye Irritation:  0.874 Respiratory Toxicity:  0.054
Drug-induced Neurotoxicity:  0.021 Ototoxicity:  0.683
Hematotoxicity:  0.12 Drug-induced Nephrotoxicity:  0.725
Genotoxicity:  0.074 RPMI-8226 Immunitoxicity:  0.141
A549 Cytotoxicity:  0.211 Hek293 Cytotoxicity:  0.09
BCF:   0.387
?
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:   2.203
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   3.575
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.013
?
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
NPO9317 Itoa orientalis Species Salicaceae Eukaryota bark, twigs, and leaves n.a. n.a. PMID[18412396]
NPO9317 Itoa orientalis Species Salicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO9317 Itoa orientalis Species Salicaceae 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
NPT31 Individual protein Cyclooxygenase-2 Homo sapiens Inhibition = 40.0 % PubChem BioAssay data set

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





 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 NPC9248 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
0.6977 Remote Similarity NPC228907
0.6739 Remote Similarity NPC142319
0.66 Remote Similarity NPC221090
0.6471 Remote Similarity NPC166168
0.6415 Remote Similarity NPC205054
0.6415 Remote Similarity NPC19470
0.6296 Remote Similarity NPC481303
0.625 Remote Similarity NPC484157
0.6122 Remote Similarity NPC192810
0.6071 Remote Similarity NPC25292
0.6 Remote Similarity NPC210015
0.6 Remote Similarity NPC106944
0.5965 Remote Similarity NPC59324
0.5862 Remote Similarity NPC100389
0.5862 Remote Similarity NPC190714
0.5769 Remote Similarity NPC226712
0.5769 Remote Similarity NPC608788
0.5741 Remote Similarity NPC40377
0.5741 Remote Similarity NPC310661
0.5714 Remote Similarity NPC212729
0.5714 Remote Similarity NPC604498
0.569 Remote Similarity NPC473045
0.5686 Remote Similarity NPC152722
0.5667 Remote Similarity NPC186418
0.5667 Remote Similarity NPC202700
0.566 Remote Similarity NPC145900
0.5614 Remote Similarity NPC105827
0.5606 Remote Similarity NPC232228
0.56 Remote Similarity NPC269242
0.5593 Remote Similarity NPC99515
0.5556 Remote Similarity NPC116229
0.5556 Remote Similarity NPC214454
0.5536 Remote Similarity NPC83975
0.55 Remote Similarity NPC469661
0.55 Remote Similarity NPC65530
0.549 Remote Similarity NPC153149
0.549 Remote Similarity NPC294470
0.5472 Remote Similarity NPC12308
0.54 Remote Similarity NPC276195
0.5385 Remote Similarity NPC25817
0.5385 Remote Similarity NPC191046
0.5323 Remote Similarity NPC175976
0.5294 Remote Similarity NPC217854
0.5283 Remote Similarity NPC60589
0.5283 Remote Similarity NPC469708
0.5283 Remote Similarity NPC604439
0.5283 Remote Similarity NPC609376
0.5263 Remote Similarity NPC23084
0.5254 Remote Similarity NPC222455
0.5246 Remote Similarity NPC174377
0.5185 Remote Similarity NPC200092
0.5172 Remote Similarity NPC214910
0.5172 Remote Similarity NPC26080
0.5172 Remote Similarity NPC165686
0.5167 Remote Similarity NPC97326
0.5167 Remote Similarity NPC34456
0.5161 Remote Similarity NPC41844
0.5161 Remote Similarity NPC37074
0.5161 Remote Similarity NPC479374
0.5152 Remote Similarity NPC45400
0.5091 Remote Similarity NPC80098
0.5085 Remote Similarity NPC57751
0.5085 Remote Similarity NPC473044
0.5082 Remote Similarity NPC478871
0.5082 Remote Similarity NPC478870
0.5082 Remote Similarity NPC199335
0.5082 Remote Similarity NPC478872
0.5082 Remote Similarity NPC475628
0.5082 Remote Similarity NPC478873
0.5082 Remote Similarity NPC477240
0.5079 Remote Similarity NPC212670
0.5079 Remote Similarity NPC121001
0.5079 Remote Similarity NPC287780
0.5079 Remote Similarity NPC206264
0.5079 Remote Similarity NPC60982
0.5079 Remote Similarity NPC87696
0.5077 Remote Similarity NPC165720
0.5075 Remote Similarity NPC217950

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC9248 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
0.5769 Remote Similarity NPD1091 Pre-clinical
0.5079 Remote Similarity NPD1653 Approved

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