Natural Product: NPC100389

Natural Product IDNPC100389
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Methyl 4-O-Beta-D-Glucopyranosylcaffeate
IUPAC Name methyl (E)-3-[3-hydroxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]prop-2-enoate
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL482045
PubChem CID 12311282
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 RHLLCIWGXNNMLI-BJGSYIFTSA-N
Standard InCHI InChI=1S/C16H20O9/c1-23-12(19)5-3-8-2-4-10(9(18)6-8)24-16-15(22)14(21)13(20)11(7-17)25-16/h2-6,11,13-18,20-22H,7H2,1H3/b5-3+/t11-,13-,14+,15-,16-/m1/s1
SMILES COC(=O)/C=C/c1ccc(c(c1)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   356.11 Volume:   334.109
?
Van der Waals volume.
Dense:   1.066 LogP:   -0.114
?
The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.61
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -1.789
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   6.0 Rigid Bonds:   14.0
TPSA:   145.91
?
Topological Polar Surface Area.
 H-Bond Acceptor:   9.0
H-Bond Donor:   5.0 Rings:   2.0
Heavy Atoms:   9.0

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:   3.666 Fsp3:   0.438
MCE-18:   51.522
?
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:   0.644 Fluc inhibitor:   0.744
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.27
?
The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.357
?
The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.267 Promiscuous compounds:   0.379

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.089 MDCK Permeability:   -5.21
Pgp-inhibitor:   0.002 Pgp-substrate:   0.092
PAMPA:   0.966
?
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):   0.835
20% Bioavailability (F20%):   0.823 30% Bioavailability (F30%):   0.996
50% Bioavailability (F50%):   0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.036 MRP1:   0.018
Plasma Protein Binding (PPB):   71.333% Volume Distribution (VD):   -0.316
Fu: 28.122%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.999
OATP1B3 inhibitor:   1.0 BCRP inhibitor:   0.043
BSEP inhibitor:   0.007

ADMET: Metabolism

CYP1A2-inhibitor:   0.002 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.002
CYP2C9-inhibitor:   0.0 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.0 CYP2D6-substrate:   0.001
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.316
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.999
HLM stability:   0.01
?
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):  2.858 Half-life (T1/2):  2.946

ADMET: Toxicity

hERG Blockers:  0.021 hERG Blockers (10um):  0.098
Human Hepatotoxicity (H-HT):  0.622 Drug-induced Liver Injury (DILI):  0.753
AMES Toxicity:  0.867 Rat Oral Acute Toxicity:  0.017
Maximum Recommended Daily Dose:  0.038 Skin Sensitization:  0.998
Carcinogencity:  0.216 Eye Corrosion:  0.001
Eye Irritation:  0.482 Respiratory Toxicity:  0.008
Drug-induced Neurotoxicity:  0.008 Ototoxicity:  0.845
Hematotoxicity:  0.164 Drug-induced Nephrotoxicity:  0.718
Genotoxicity:  0.111 RPMI-8226 Immunitoxicity:  0.079
A549 Cytotoxicity:  0.107 Hek293 Cytotoxicity:  0.127
BCF:   0.417
?
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:   3.037
?
48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.619
?
48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.864
?
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
NPO14305 Moricandia arvensis Species Brassicaceae Eukaryota n.a. n.a. n.a. PMID[15844940]
NPO14305 Moricandia arvensis Species Brassicaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO14305 Moricandia arvensis Species Brassicaceae 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
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. Activity = 0.89 mM PMID[15844940]
NPT20529 Non-molecular NON-PROTEIN TARGET n.a. IC50 = 486.2 ug.mL-1 PMID[15844940]

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 NPC100389 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
0.8596 High Similarity NPC202700
0.8182 Intermediate Similarity NPC481303
0.7679 Intermediate Similarity NPC604356
0.7097 Intermediate Similarity NPC186418
0.7097 Intermediate Similarity NPC185778
0.6885 Remote Similarity NPC59324
0.6667 Remote Similarity NPC476864
0.6575 Remote Similarity NPC476866
0.6533 Remote Similarity NPC476865
0.6522 Remote Similarity NPC310064
0.65 Remote Similarity NPC19470
0.6377 Remote Similarity NPC488085
0.6324 Remote Similarity NPC186406
0.6197 Remote Similarity NPC232228
0.6119 Remote Similarity NPC98777
0.6 Remote Similarity NPC157554
0.5932 Remote Similarity NPC200092
0.589 Remote Similarity NPC292443
0.5862 Remote Similarity NPC9248
0.5806 Remote Similarity NPC232880
0.5753 Remote Similarity NPC145319
0.5658 Remote Similarity NPC199928
0.5658 Remote Similarity NPC476867
0.5641 Remote Similarity NPC476868
0.5634 Remote Similarity NPC88043
0.5625 Remote Similarity NPC26080
0.5625 Remote Similarity NPC210015
0.5625 Remote Similarity NPC165686
0.5556 Remote Similarity NPC191046
0.5541 Remote Similarity NPC166180
0.5538 Remote Similarity NPC248355
0.5538 Remote Similarity NPC105827
0.5469 Remote Similarity NPC251102
0.5469 Remote Similarity NPC205054
0.5469 Remote Similarity NPC210298
0.5455 Remote Similarity NPC55040
0.5455 Remote Similarity NPC25292
0.5441 Remote Similarity NPC294166
0.5441 Remote Similarity NPC115022
0.5441 Remote Similarity NPC65530
0.5429 Remote Similarity NPC106944
0.5397 Remote Similarity NPC11724
0.5397 Remote Similarity NPC310661
0.5373 Remote Similarity NPC302378
0.5362 Remote Similarity NPC604095
0.5323 Remote Similarity NPC221090
0.5316 Remote Similarity NPC476869
0.5303 Remote Similarity NPC479029
0.5278 Remote Similarity NPC116229
0.5278 Remote Similarity NPC606353
0.527 Remote Similarity NPC72249
0.5254 Remote Similarity NPC484157
0.5246 Remote Similarity NPC60589
0.5246 Remote Similarity NPC469708
0.5231 Remote Similarity NPC479028
0.5231 Remote Similarity NPC479031
0.5211 Remote Similarity NPC189115
0.5211 Remote Similarity NPC212770
0.5176 Remote Similarity NPC469654
0.5167 Remote Similarity NPC192810
0.5152 Remote Similarity NPC210478
0.5147 Remote Similarity NPC473045
0.5143 Remote Similarity NPC37468
0.5139 Remote Similarity NPC259767
0.5122 Remote Similarity NPC26928
0.5119 Remote Similarity NPC89693
0.5085 Remote Similarity NPC212729
0.5085 Remote Similarity NPC142319
0.5085 Remote Similarity NPC604498
0.5077 Remote Similarity NPC49074
0.5072 Remote Similarity NPC307110
0.5057 Remote Similarity NPC44507

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC100389 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