Natural Product: NPC268193

Natural Product IDNPC268193
Common Name
?
The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
 Kaempferol-6-C-Beta-D-Glucopyranoside
IUPAC Name 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-6-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]chromen-4-one
Synonyms
Synthetic Gene Cluster n.a.
ChEMBL Identifier CHEMBL552215
PubChem CID 24721625
Chemical Classification
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000261] Phenylpropanoids and polyketides
      • [CHEMONTID:0000334] Flavonoids
        • [CHEMONTID:0001111] Flavonoid glycosides
          • [CHEMONTID:0001737] Flavonoid C-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 SUZADCRUSDZVCH-DSTJRUDUSA-N
Standard InCHI InChI=1S/C21H20O11/c22-6-11-14(25)17(28)19(30)21(32-11)12-9(24)5-10-13(15(12)26)16(27)18(29)20(31-10)7-1-3-8(23)4-2-7/h1-5,11,14,17,19,21-26,28-30H,6H2/t11-,14-,17+,19-,21+/m1/s1
SMILES OC[C@H]1O[C@H]([C@@H]([C@H]([C@@H]1O)O)O)c1c(O)cc2c(c1O)c(=O)c(c(o2)c1ccc(cc1)O)O

  Calculated Properties

Physi-Chem Properties

Molecular Weight:   448.1 Volume:   413.147
?
Van der Waals volume.
Dense:   1.085 LogP:   0.45
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The logarithm of the n-octanol/water distribution coefficients.
logD7.4:   0.954
?
The logarithm of the n-octanol/water distribution coefficient at pH=7.4.
 LogS:   -3.789
?
The logarithm of aqueous solubility value.
Rotatable Bonds:   3.0 Rigid Bonds:   24.0
TPSA:   201.28
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Topological Polar Surface Area.
 H-Bond Acceptor:   11.0
H-Bond Donor:   8.0 Rings:   4.0
Heavy Atoms:   11.0

MedChem Properties

QED Drug-Likeness Score:   0.264 GASA:   1.0
?
GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:   4.038 Fsp3:   0.286
MCE-18:   91.0
?
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:   Rejected BMS Rule:   0
Chelating Alert:   1 PAINS Alert:   0
Colloidal aggregators:   0.599 Fluc inhibitor:   0.191
?
The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:   0.815
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The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1
 Green fluorescence:   0.612
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The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:   0.274 Promiscuous compounds:   0.583

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:   -6.287 MDCK Permeability:   -4.94
Pgp-inhibitor:   0.0 Pgp-substrate:   0.347
PAMPA:   1.0
?
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):   0.771
20% Bioavailability (F20%):   0.145 30% Bioavailability (F30%):   0.973
50% Bioavailability (F50%):   0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):   0.0 MRP1:   0.789
Plasma Protein Binding (PPB):   88.127% Volume Distribution (VD):   -0.2
Fu: 8.519%
?
The fraction unbound in plasms.
 OATP1B1 inhibitor:   0.151
OATP1B3 inhibitor:   0.996 BCRP inhibitor:   0.099
BSEP inhibitor:   0.14

ADMET: Metabolism

CYP1A2-inhibitor:   0.0 CYP1A2-substrate:   0.0
CYP2C19-inhibitor:   0.0 CYP2C19-substrate:   0.173
CYP2C9-inhibitor:   0.021 CYP2C9-substrate:   0.0
CYP2D6-inhibitor:   0.008 CYP2D6-substrate:   0.061
CYP3A4-inhibitor:   0.0 CYP3A4-substrate:   0.0
CYP2B6-substrate:   0.0 CYP2C8-inhibitor:   0.996
HLM stability:   0.355
?
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):  3.531 Half-life (T1/2):  4.339

ADMET: Toxicity

hERG Blockers:  0.018 hERG Blockers (10um):  0.135
Human Hepatotoxicity (H-HT):  0.501 Drug-induced Liver Injury (DILI):  0.86
AMES Toxicity:  0.72 Rat Oral Acute Toxicity:  0.095
Maximum Recommended Daily Dose:  0.178 Skin Sensitization:  0.974
Carcinogencity:  0.251 Eye Corrosion:  0.0
Eye Irritation:  0.861 Respiratory Toxicity:  0.052
Drug-induced Neurotoxicity:  0.004 Ototoxicity:  0.66
Hematotoxicity:  0.067 Drug-induced Nephrotoxicity:  0.093
Genotoxicity:  0.908 RPMI-8226 Immunitoxicity:  0.073
A549 Cytotoxicity:  0.401 Hek293 Cytotoxicity:  0.497
BCF:   0.397
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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:   2.945
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48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:   4.266
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48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].
 LC50FM:   3.642
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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
NPO7764 Ulmus wallichiana Species Ulmaceae Eukaryota n.a. n.a. n.a. PMID[19596573]
NPO15288 Zelkova serrata Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[COCONUT]
NPO7764 Ulmus wallichiana Species Ulmaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO10904 Panax arboreus Species Araliaceae Eukaryota n.a. n.a. n.a. Database[UNPD]
NPO15288 Zelkova serrata Species Ulmaceae 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
NPT839 Cell line L6 Rattus norvegicus Activity = 12.2 % PMID[21129962]

In vivo activity

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 16.7 % PMID[21129962]
NPT29 Organism Rattus norvegicus Rattus norvegicus Activity = 23.5 % PMID[21129962]





 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 NPC268193 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
0.8769 High Similarity NPC289771
0.7826 Intermediate Similarity NPC328740
0.7826 Intermediate Similarity NPC289774
0.7162 Intermediate Similarity NPC304745
0.6986 Remote Similarity NPC53545
0.6386 Remote Similarity NPC47923
0.6377 Remote Similarity NPC10097
0.6375 Remote Similarity NPC111249
0.6104 Remote Similarity NPC112701
0.5909 Remote Similarity NPC473042
0.589 Remote Similarity NPC139966
0.5747 Remote Similarity NPC218488
0.5698 Remote Similarity NPC603300
0.5658 Remote Similarity NPC228383
0.5658 Remote Similarity NPC239644
0.5641 Remote Similarity NPC209846
0.5595 Remote Similarity NPC326592
0.5488 Remote Similarity NPC10807
0.5488 Remote Similarity NPC161881
0.5412 Remote Similarity NPC109594
0.5342 Remote Similarity NPC24821
0.5181 Remote Similarity NPC323593
0.5181 Remote Similarity NPC203500
0.5119 Remote Similarity NPC84265
0.5111 Remote Similarity NPC604854
0.5062 Remote Similarity NPC611357
0.5056 Remote Similarity NPC472607

Similar Clinical/Approved Drugs

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

●  The left chart: Distribution of similarity level between NPC268193 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